# Doing Science...

100%

# Variant Report

Save HTML archive

Curation

## Filtering Variants

Showing variants that contain the term

## Conditions reviewed by experts

Below are conditions that were reviewed by an expert panel and/or are in the Genetic Testing Registry (GTR) according to ClinVar. The data presented does not diagnose disease and has no guarantees of reporting accuracy. We report heterozygous variants as yellow and homozygous variants as red. A red or yellow variant does not necessarily mean one has or carries a condition or disease. This is for research and educational purposes only.

Gene: MTHFR
Variant: c.1286A>C
(p.Glu429Ala)
rsID: rs1801131
Ref Allele: T
Alt Allele: G
Freq: 24.9092%
CADD: 19.91

ClinVar Submissions (6)

- Gastrointestinal stroma tumor

  ### Gastrointestinal stroma tumor

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 02, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 6
  Clinical Significance: Conflicting interpretations of pathogenicity, other, risk factor
  Assembly: GRCh38
  Chromosome/Position: 1:11794419
  OMIM Allelic Variant: 607093.0004

- MTHFR deficiency, thermolabile type

  ### MTHFR deficiency, thermolabile type

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 02, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 6
  Clinical Significance: Conflicting interpretations of pathogenicity, other, risk factor
  Assembly: GRCh38
  Chromosome/Position: 1:11794419
  OMIM Allelic Variant: 607093.0004

- Neural tube defects, folate-sensitive

  ### Neural tube defects, folate-sensitive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 02, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 6
  Clinical Significance: Conflicting interpretations of pathogenicity, other, risk factor
  Assembly: GRCh38
  Chromosome/Position: 1:11794419
  OMIM Allelic Variant: 607093.0004

- Schizophrenia, susceptibility to

  ### Schizophrenia, susceptibility to

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 02, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 6
  Clinical Significance: Conflicting interpretations of pathogenicity, other, risk factor
  Assembly: GRCh38
  Chromosome/Position: 1:11794419
  OMIM Allelic Variant: 607093.0004

- not provided

  ### not provided

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 02, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 6
  Clinical Significance: Conflicting interpretations of pathogenicity, other, risk factor
  Assembly: GRCh38
  Chromosome/Position: 1:11794419
  OMIM Allelic Variant: 607093.0004

- not specified

  ### not specified

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 02, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 6
  Clinical Significance: Conflicting interpretations of pathogenicity, other, risk factor
  Assembly: GRCh38
  Chromosome/Position: 1:11794419
  OMIM Allelic Variant: 607093.0004

Expert Reviewed Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (312)

Homo

GG

Gene: CCDC170
Variant: g.151627231G>A
rsID: rs2046210
Ref Allele: G
Alt Allele: A
Freq: 42.4017%
CADD: 0.277

ClinVar Submissions (1)

- Estrogen resistance, Autosomal recessive

  ### Estrogen resistance

  Estrogen resistance (ESTRR) is characterized by absence of puberty with elevated estradiol and gonadotropic hormones, as well as markedly delayed bone maturation. Female patients show absent breast development, small uterus, and enlarged multicystic ovaries; male patients may show small testes (Bernard et al., 2017). Some patients exhibit continued growth into adulthood (Smith et al., 1994).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 01, 2014
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Likely pathogenic
  Assembly: GRCh38
  Chromosome/Position: 6:151627231

Expert Reviewed Clinically Significant Likely pathogenic

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (88)

Hetero

GA

Gene: GALT
Variant: c.940A>G
(p.Asn314Asp)
rsID: rs2070074
Ref Allele: A
Alt Allele: G
Freq: 6.6665%
CADD: 20.3

ClinVar Submissions (13)

- Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase

  ### Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 13, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 13
  Clinical Significance: Conflicting interpretations of pathogenicity, other
  Assembly: GRCh38
  Chromosome/Position: 9:34649445
  OMIM Allelic Variant: 606999.0005

- Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase

  ### Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 13, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 13
  Clinical Significance: Conflicting interpretations of pathogenicity, other
  Assembly: GRCh38
  Chromosome/Position: 9:34649445
  OMIM Allelic Variant: 606999.0005

- GALT POLYMORPHISM (DUARTE, D2)

  ### GALT POLYMORPHISM (DUARTE, D2)

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 13, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 13
  Clinical Significance: Conflicting interpretations of pathogenicity, other
  Assembly: GRCh38
  Chromosome/Position: 9:34649445
  OMIM Allelic Variant: 606999.0005

- GALT POLYMORPHISM (LOS ANGELES, D1)

  ### GALT POLYMORPHISM (LOS ANGELES, D1)

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 13, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 13
  Clinical Significance: Conflicting interpretations of pathogenicity, other
  Assembly: GRCh38
  Chromosome/Position: 9:34649445
  OMIM Allelic Variant: 606999.0005

- Galactosemia

  ### Galactosemia

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 13, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 13
  Clinical Significance: Conflicting interpretations of pathogenicity, other
  Assembly: GRCh38
  Chromosome/Position: 9:34649445
  OMIM Allelic Variant: 606999.0005

- not provided

  ### not provided

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 13, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 13
  Clinical Significance: Conflicting interpretations of pathogenicity, other
  Assembly: GRCh38
  Chromosome/Position: 9:34649445
  OMIM Allelic Variant: 606999.0005

- not specified

  ### not specified

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 13, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 13
  Clinical Significance: Conflicting interpretations of pathogenicity, other
  Assembly: GRCh38
  Chromosome/Position: 9:34649445
  OMIM Allelic Variant: 606999.0005

Low clinical importance, Uncertain benign — This variant has an allele frequency of ~8% and is ancestral to "Duarte" / "Duarte 2" and "Duarte 1"/"Los Angeles" galactosemia variants. This variant is evolutionarily ancestral, and in vitro studies fail to support an impact of this variant on enzyme activity. Carney et al. instead implicate a 4 base deletion on the 5' of the GALT gene as being causal and linked to this variant. Galactosemia is typically screened and detected in infants and causes early, severe but nonspecific symptoms (digestive problems, lethargy, failure to thrive).

Expert Reviewed Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (28)

Hetero

AG

Gene: GALT
Variant: c.652C>T
(p.Leu218=)
rsID: rs2070075
Ref Allele: C
Alt Allele: T
Freq: 2.2888%uncommon
CADD: 15.26

ClinVar Submissions (9)

- Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase

  ### Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 11, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign, other
  Assembly: GRCh38
  Chromosome/Position: 9:34648421
  OMIM Allelic Variant: 606999.0012

- GALT POLYMORPHISM (LOS ANGELES, D1)

  ### GALT POLYMORPHISM (LOS ANGELES, D1)

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 11, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign, other
  Assembly: GRCh38
  Chromosome/Position: 9:34648421
  OMIM Allelic Variant: 606999.0012

- Galactosemia

  ### Galactosemia

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 11, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign, other
  Assembly: GRCh38
  Chromosome/Position: 9:34648421
  OMIM Allelic Variant: 606999.0012

- not provided

  ### not provided

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 11, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign, other
  Assembly: GRCh38
  Chromosome/Position: 9:34648421
  OMIM Allelic Variant: 606999.0012

Expert Reviewed Benign/Likely benign, other

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (10)

Hetero

CT

Gene: LCT;MCM6
Variant: c.-13907C>T
rsID: rs4988235
Ref Allele: G
Alt Allele: A
Freq: 38.7662%
CADD: 10.75

ClinVar Submissions (1)

- Lactase persistence

  ### Lactase persistence

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 20, 2018
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: association
  Assembly: GRCh38
  Chromosome/Position: 2:135851076
  OMIM Allelic Variant: 601806.0001

Expert Reviewed

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (70)

Hetero

GA

Gene: AMPD1
Variant: c.133C>T
(p.Gln45Ter)
rsID: rs17602729
Ref Allele: G
Alt Allele: A
Freq: 8.0697%
CADD: 36

ClinVar Submissions (6)

- Muscle AMP deaminase deficiency, Autosomal recessive

  ### Muscle AMP deaminase deficiency

  Myoadenylate deaminase deficiency (MMDD) is an autosomal recessive condition that can manifest as exercise-induced muscle pain, occasionally associated with rhabdomyolysis and/or increased serum creatine kinase, or even infantile hypotonia. However, the finding of homozygous mutations among asymptomatic individuals have suggested to some (e.g., Verzijl et al., 1998) that AMPD1 deficiency may be a harmless entity (summary by Castro-Gago et al., 2011). Genetta et al. (2001) stated that AMPD1 deficiency is the most prevalent genetic disease in humans, the number of people heterozygous approaching 10% of Caucasians and individuals of African descent (Sabina et al., 1989). A small percentage of homozygous-deficient individuals, approximately 1.8% of the population, display symptoms of chronic fatigue and lost productivity as well as a predisposition to stress-related ailments, including heart disease and stroke, according to Genetta et al. (2001).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 27, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 6
  Clinical Significance: Conflicting interpretations of pathogenicity, other
  Assembly: GRCh38
  Chromosome/Position: 1:114693436
  OMIM Allelic Variant: 102770.0001

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 27, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 6
  Clinical Significance: Conflicting interpretations of pathogenicity, other
  Assembly: GRCh38
  Chromosome/Position: 1:114693436
  OMIM Allelic Variant: 102770.0001

Low clinical importance, Likely pathogenic — Causes Adenosine Deaminase Deficiency in a recessive manner. Most of the time individuals do not report symptoms, but when symptoms do exist they to be post-exercise symptoms of muscle weakness, muscle pain, and getting tired more quickly.

Expert Reviewed Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (17)

Homo

AA

## Drug response reviewed by experts

Below are drug responses that were reviewed by an expert panel according to ClinVar. The data presented has no guarantees of reporting accuracy. Heterozygous variants are reported as yellow and homozygous variants as red. Reference alleles may be modified to match risk. While a red or yellow variant could indicate a suboptimal response to drug, it doesn't necessarily mean one won't respond well to it. This is for research and educational purposes only.

Gene: GSTP1
Variant: c.313A>G
(p.Ile105Val)
rsID: rs1695
Ref Allele: A
Alt Allele: G
Freq: 37.0731%
CADD: 4.014

ClinVar Submissions (2)

- Neoplasm of the large intestine

  ### Neoplasm of the large intestine

  A benign or malignant neoplasm that affects the colon or rectum. Representative examples of benign neoplasms include lipoma and leiomyoma. Representative examples of malignant neoplasms include carcinoma, lymphoma, and sarcoma. Colorectal adenomas always exhibit epithelial dysplasia and are considered premalignant neoplasms.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 03, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 11:67585218

- Platinum compounds response - Toxicity/ADR

  ### Platinum compounds response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 03, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 11:67585218

- cisplatin response - Toxicity/ADR

  ### cisplatin response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 03, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 11:67585218

- cyclophosphamide and epirubicin response - Efficacy, Toxicity/ADR

  ### cyclophosphamide and epirubicin response - Efficacy, Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 03, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 11:67585218

- fluorouracil and oxaliplatin response - Efficacy

  ### fluorouracil and oxaliplatin response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 03, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 11:67585218

Insufficiently evaluated pharmacogenetic — Hematological toxicity with fluoruracil.

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- UniProt
- OpenSNP
- PubMed (265)

Homo

GG

Gene: CYP19A1
Variant: c.*161T>G
rsID: rs4646
Ref Allele: A
Alt Allele: C
Freq: 70.0545%
CADD: 0.652

ClinVar Submissions (2)

- Aromatase deficiency

  ### Aromatase deficiency

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 06, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 15:51210647

- anastrozole response - Efficacy

  ### anastrozole response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 06, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 15:51210647

- cyclophosphamide response - Efficacy

  ### cyclophosphamide response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 06, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 15:51210647

- docetaxel response - Efficacy

  ### docetaxel response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 06, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 15:51210647

- doxorubicin response - Efficacy

  ### doxorubicin response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 06, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 15:51210647

- epirubicin response - Efficacy

  ### epirubicin response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 06, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 15:51210647

- exemestane response - Efficacy

  ### exemestane response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 06, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 15:51210647

- fluorouracil response - Efficacy

  ### fluorouracil response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 06, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 15:51210647

- paclitaxel response - Efficacy

  ### paclitaxel response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 06, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 15:51210647

- radiotherapy response - Efficacy

  ### radiotherapy response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 06, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 15:51210647

- tamoxifen response - Efficacy

  ### tamoxifen response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 06, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 15:51210647

Insufficiently evaluated pharmacogenetic — associated with response to a drug letrozole in cancer patients

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (60)

Hetero

AC

Gene: SOD2
Variant: c.47T>C
(p.Val16Ala)
rsID: rs4880
Ref Allele: A
Alt Allele: G
Freq: 45.7529%
CADD: 12.94

ClinVar Submissions (2)

- Microvascular complications of diabetes 6

  ### Microvascular complications of diabetes 6

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 11, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 6:159692840
  OMIM Allelic Variant: 147460.0001

- SUPEROXIDE DISMUTASE 2 POLYMORPHISM

  ### SUPEROXIDE DISMUTASE 2 POLYMORPHISM

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 11, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 6:159692840
  OMIM Allelic Variant: 147460.0001

- cyclophosphamide response - Efficacy

  ### cyclophosphamide response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 11, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 6:159692840
  OMIM Allelic Variant: 147460.0001

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (193)

Hetero

AG

Gene: ADD1
Variant: c.1378G>T
(p.Gly460Trp)
rsID: rs4961
Ref Allele: G
Alt Allele: T
Freq: 18.0794%
CADD: 25.2

ClinVar Submissions (2)

- Hypertension, salt-sensitive essential, susceptibility to

  ### Hypertension, salt-sensitive essential, susceptibility to

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 14, 2015
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 4:2904980
  OMIM Allelic Variant: 102680.0001

- furosemide and spironolactone response - Efficacy

  ### furosemide and spironolactone response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 14, 2015
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 4:2904980
  OMIM Allelic Variant: 102680.0001

Insufficiently evaluated pathogenic — This variant is associated with salt-sensitivity in patients with hypertension.

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- UniProt
- OpenSNP
- PubMed (45)

Hetero

GT

Gene: HTR1A
Variant: c.-1019G>C
rsID: rs6295
Ref Allele: C
Alt Allele: G
Freq: 49.9873%
CADD: 2.67

ClinVar Submissions (2)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 09, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 5:63962738

- paroxetine response - Efficacy

  ### paroxetine response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 09, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 5:63962738

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (115)

Hetero

CG

Gene: VKORC1
Variant: c.*134G>A
rsID: rs7294
Ref Allele: C
Alt Allele: T
Freq: 38.4851%
CADD: 1.59

ClinVar Submissions (2)

- Vitamin K-Dependent Clotting Factors

  ### Vitamin K-Dependent Clotting Factors

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 11, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 16:31091000

- acenocoumarol response - Dosage

  ### acenocoumarol response - Dosage

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 11, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 16:31091000

- phenprocoumon response - Dosage

  ### phenprocoumon response - Dosage

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 11, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 16:31091000

- warfarin response - Dosage

  ### warfarin response - Dosage

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 11, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 16:31091000

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (73)

Hetero

CT

Gene: ERCC1
Variant: c.354T>C
(p.Asn118=)
rsID: rs11615
Ref Allele: A
Alt Allele: G
Freq: 57.5449%
CADD: 1.504

ClinVar Submissions (2)

- Platinum compounds response - Efficacy, Toxicity/ADR

  ### Platinum compounds response - Efficacy, Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 06, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 19:45420395

- Xeroderma pigmentosum

  ### Xeroderma pigmentosum

  Xeroderma pigmentosum (XP) is characterized by: Sun sensitivity (severe sunburn with blistering, persistent erythema on minimal sun exposure in ~60% of affected individuals), with marked freckle-like pigmentation of the face before age two years in most affected individuals; Sunlight-induced ocular involvement (photophobia, keratitis, atrophy of the skin of the lids); Greatly increased risk of sunlight-induced cutaneous neoplasms (basal cell carcinoma, squamous cell carcinoma, melanoma). Approximately 25% of affected individuals have neurologic manifestations (acquired microcephaly, diminished or absent deep tendon stretch reflexes, progressive sensorineural hearing loss, and progressive cognitive impairment). The most common causes of death are skin cancer, neurologic degeneration, and internal cancer. The median age at death in persons with XP with neurodegeneration (29 years) was found to be younger than that in persons with XP without neurodegeneration (37 years).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 06, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 19:45420395

- carboplatin response - Efficacy, Toxicity/ADR

  ### carboplatin response - Efficacy, Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 06, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 19:45420395

- cisplatin response - Efficacy, Toxicity/ADR

  ### cisplatin response - Efficacy, Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 06, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 19:45420395

- oxaliplatin response - Efficacy, Toxicity/ADR

  ### oxaliplatin response - Efficacy, Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 06, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 19:45420395

- platinum response - Efficacy, Toxicity/ADR

  ### platinum response - Efficacy, Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 06, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 19:45420395

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (125)

Hetero

AG

Gene: KIF6
Variant: c.2155T>C
(p.Trp719Arg)
rsID: rs20455
Ref Allele: A
Alt Allele: G
Freq: 50.0892%
CADD: 3.411

ClinVar Submissions (1)

- atorvastatin response - Efficacy

  ### atorvastatin response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 11, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 6:39357302

- pravastatin response - Efficacy

  ### pravastatin response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 11, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 6:39357302

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (30)

Hetero

AG

Gene: XRCC1
Variant: c.1196A>G
(p.Gln399Arg)
rsID: rs25487
Ref Allele: T
Alt Allele: C
Freq: 71.5477%
CADD: 17.31

ClinVar Submissions (1)

- Platinum compounds response - Efficacy

  ### Platinum compounds response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 07, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 19:43551574

- carboplatin response - Efficacy

  ### carboplatin response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 07, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 19:43551574

- cisplatin response - Efficacy

  ### cisplatin response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 07, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 19:43551574

- oxaliplatin response - Efficacy

  ### oxaliplatin response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 07, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 19:43551574

- platinum response - Efficacy

  ### platinum response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 07, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 19:43551574

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (234)

Hetero

TC

Gene: FCGR3A
Variant: c.526T>G
(p.Phe176Val)
rsID: rs396991
Ref Allele: A
Alt Allele: C
Freq: 33.5786%
CADD: 0.104

ClinVar Submissions (2)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 11, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 1:161544752

- rituximab response - Efficacy

  ### rituximab response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 11, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 1:161544752

- trastuzumab response - Efficacy

  ### trastuzumab response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 11, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 1:161544752

Insufficiently evaluated pharmacogenetic — Better response with cetuximab and rituximab.

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- UniProt
- OpenSNP
- PubMed (55)

Hetero

AC

Gene: MC4R
Variant: g.60215554C>A
rsID: rs489693
Ref Allele: C
Alt Allele: A
Freq: 34.9667%
CADD: 0.12

ClinVar Submissions (1)

- amisulpride response - Toxicity/ADR

  ### amisulpride response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 22, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 18:60215554

- aripiprazole response - Toxicity/ADR

  ### aripiprazole response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 22, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 18:60215554

- clozapine response - Toxicity/ADR

  ### clozapine response - Toxicity/ADR

  Clozapine is one of the most effective antipsychotics available in the treatment of schizophrenia and the only antipsychotic found to be effective in treatment-resistant schizophrenia. Clozapine is also used to reduce the risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder. Compared to typical antipsychotics, clozapine is far less likely to cause movement disorders, known as extrapyramidal side effects, which include dystonia, akathisia, parkinsonism, and tardive dyskinesia. However, there are significant risks associated with clozapine therapy that limits its use to only the most severely ill patients who have not responded adequately to standard drug therapy. Most notably, because of the risk of clozapine-induced agranulocytosis, clozapine treatment requires monitoring of white blood counts and absolute neutrophil counts, and in the US, the FDA requires that patients receiving clozapine be enrolled in a computer-based registry. Clozapine is metabolized in the liver by the cytochrome P450 (CYP) system of enzymes. CYP1A2 is the main CYP isoform in clozapine metabolism and CYP1A2 activity is an important determinant of clozapine dose. Other CYP enzymes involved in clozapine metabolism include CYP2D6 and CYP3A4. Approximately 6-10% of Caucasians have reduced activity of CYP2D6 ("poor metabolizers"). These individuals may develop higher than expected plasma concentrations of clozapine with usual doses. The FDA-approved drug label for clozapine states that a dose reduction may be necessary in patients who are CYP2D6 poor metabolizers.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 22, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 18:60215554

- haloperidol response - Toxicity/ADR

  ### haloperidol response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 22, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 18:60215554

- olanzapine response - Toxicity/ADR

  ### olanzapine response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 22, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 18:60215554

- paliperidone response - Toxicity/ADR

  ### paliperidone response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 22, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 18:60215554

- quetiapine response - Toxicity/ADR

  ### quetiapine response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 22, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 18:60215554

- risperidone response - Toxicity/ADR

  ### risperidone response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 22, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 18:60215554

- ziprasidone response - Toxicity/ADR

  ### ziprasidone response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 22, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 18:60215554

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (13)

Homo

AA

Gene: APOA5
Variant: c.-644C>T
rsID: rs662799
Ref Allele: G
Alt Allele: A
Freq: 89.5929%
CADD: 3.29

ClinVar Submissions (1)

- atorvastatin response - Efficacy

  ### atorvastatin response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 14, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 11:116792991

- lovastatin response - Efficacy

  ### lovastatin response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 14, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 11:116792991

- simvastatin response - Efficacy

  ### simvastatin response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 14, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 11:116792991

Insufficiently evaluated pharmacogenetic — associated with the triglyceride levels and the risk of first heart attack

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (120)

Homo

AA

Gene: DYNC2H1
Variant: g.103547430A>G
rsID: rs716274
Ref Allele: A
Alt Allele: G
Freq: 49.5676%
CADD: 2.369

ClinVar Submissions (1)

- Platinum compounds response - Toxicity/ADR

  ### Platinum compounds response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 14, 2015
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 11:103547430

- etoposide response - Toxicity/ADR

  ### etoposide response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 14, 2015
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 11:103547430

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (4)

Hetero

AG

Gene: LTC4S
Variant: c.-444A>C
rsID: rs730012
Ref Allele: A
Alt Allele: C
Freq: 20.467%
CADD: 0.694

ClinVar Submissions (1)

- aspirin response - Toxicity/ADR

  ### aspirin response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 28, 2015
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 5:179793637

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (26)

Homo

CC

Gene: PNPLA3
Variant: c.444C>G
(p.Ile148Met)
rsID: rs738409
Ref Allele: C
Alt Allele: G
Freq: 23.0656%
CADD: 15.61

ClinVar Submissions (2)

- Susceptibility to Nonalcoholic Fatty Liver Disease

  ### Susceptibility to Nonalcoholic Fatty Liver Disease

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 27, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 22:43928847

- asparaginase response - Toxicity/ADR

  ### asparaginase response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 27, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 22:43928847

- cyclophosphamide response - Toxicity/ADR

  ### cyclophosphamide response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 27, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 22:43928847

- daunorubicin response - Toxicity/ADR

  ### daunorubicin response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 27, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 22:43928847

- prednisolone response - Toxicity/ADR

  ### prednisolone response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 27, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 22:43928847

- vincristine response - Toxicity/ADR

  ### vincristine response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 27, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 22:43928847

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- UniProt
- OpenSNP
- PubMed (245)

Hetero

CG

Gene: CCHCR1
Variant: c.1581-597T>C
rsID: rs746647
Ref Allele: A
Alt Allele: G
Freq: 28.1162%
CADD: 5.566

ClinVar Submissions (1)

- nevirapine response - Toxicity/ADR

  ### nevirapine response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 22, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 6:31146405

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (5)

Hetero

AG

Gene: UGT1A1
Variant: c.-364C>T
rsID: rs887829
Ref Allele: C
Alt Allele: T
Freq: 34.8847%
CADD: 8.026

ClinVar Submissions (1)

- atazanavir response - Other

  ### atazanavir response - Other

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 23, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 2:233759924

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (43)

Hetero

CT

Gene: TP53
Variant: c.215C>G
(p.Pro72Arg)
rsID: rs1042522
Ref Allele: G
Alt Allele: C
Freq: 61.6654%
CADD: 6.813

ClinVar Submissions (15)

- CODON 72 POLYMORPHISM

  ### CODON 72 POLYMORPHISM

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 18, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 15
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 17:7676154
  OMIM Allelic Variant: 191170.0005

- Hereditary cancer-predisposing syndrome

  ### Hereditary cancer-predisposing syndrome

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 18, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 15
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 17:7676154
  OMIM Allelic Variant: 191170.0005

- Li-Fraumeni syndrome

  ### Li-Fraumeni syndrome

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 18, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 15
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 17:7676154
  OMIM Allelic Variant: 191170.0005

- Li-Fraumeni syndrome 1

  ### Li-Fraumeni syndrome 1

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 18, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 15
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 17:7676154
  OMIM Allelic Variant: 191170.0005

- antineoplastic agents response - Efficacy, Toxicity/ADR

  ### antineoplastic agents response - Efficacy, Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 18, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 15
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 17:7676154
  OMIM Allelic Variant: 191170.0005

- cisplatin response - Efficacy, Toxicity/ADR

  ### cisplatin response - Efficacy, Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 18, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 15
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 17:7676154
  OMIM Allelic Variant: 191170.0005

- cyclophosphamide response - Efficacy, Toxicity/ADR

  ### cyclophosphamide response - Efficacy, Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 18, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 15
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 17:7676154
  OMIM Allelic Variant: 191170.0005

- fluorouracil response - Efficacy, Toxicity/ADR

  ### fluorouracil response - Efficacy, Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 18, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 15
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 17:7676154
  OMIM Allelic Variant: 191170.0005

- not provided

  ### not provided

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 18, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 15
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 17:7676154
  OMIM Allelic Variant: 191170.0005

- not specified

  ### not specified

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 18, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 15
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 17:7676154
  OMIM Allelic Variant: 191170.0005

- paclitaxel response - Efficacy, Toxicity/ADR

  ### paclitaxel response - Efficacy, Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 18, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 15
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 17:7676154
  OMIM Allelic Variant: 191170.0005

Low clinical importance, Uncertain pathogenic — This is a common variant was first reported as a polymorphism. It has since had mixed associations with cancer: Storey et al. conclude a 7x *increased* risk of HPV cancer for homozygotes vs hets, but Jones et al. find a 1.98x *decreased* risk for colorectal cancer. This variant may have significant impact on particular cancers, but it is unclear what effect it has on the overall burden of cancer.

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (257)

Homo

CC

Gene: ABCB1
Variant: c.3435T>C
(p.Ile1145=)
rsID: rs1045642
Ref Allele: A
Alt Allele: G
Freq: 59.2492%
CADD: 0.015

ClinVar Submissions (3)

- MDR1 POLYMORPHISM

  ### MDR1 POLYMORPHISM

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 24, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 7:87509329
  OMIM Allelic Variant: 171050.0002

- Non-small cell lung cancer

  ### Non-small cell lung cancer

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 24, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 7:87509329
  OMIM Allelic Variant: 171050.0002

- digoxin response - Other

  ### digoxin response - Other

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 24, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 7:87509329
  OMIM Allelic Variant: 171050.0002

- fentanyl response - Dosage, Efficacy

  ### fentanyl response - Dosage, Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 24, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 7:87509329
  OMIM Allelic Variant: 171050.0002

- methadone response - Dosage, Efficacy

  ### methadone response - Dosage, Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 24, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 7:87509329
  OMIM Allelic Variant: 171050.0002

- methotrexate response - Toxicity/ADR

  ### methotrexate response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 24, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 7:87509329
  OMIM Allelic Variant: 171050.0002

- morphine response - Dosage, Efficacy

  ### morphine response - Dosage, Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 24, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 7:87509329
  OMIM Allelic Variant: 171050.0002

- nevirapine response - Toxicity/ADR

  ### nevirapine response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 24, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 7:87509329
  OMIM Allelic Variant: 171050.0002

- ondansetron response - Efficacy

  ### ondansetron response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 24, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 7:87509329
  OMIM Allelic Variant: 171050.0002

- opioids response - Dosage, Efficacy

  ### opioids response - Dosage, Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 24, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 7:87509329
  OMIM Allelic Variant: 171050.0002

- oxycodone response - Dosage, Efficacy

  ### oxycodone response - Dosage, Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 24, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 7:87509329
  OMIM Allelic Variant: 171050.0002

- tramadol response - Dosage, Efficacy

  ### tramadol response - Dosage, Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 24, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 7:87509329
  OMIM Allelic Variant: 171050.0002

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (428)

Homo

GG

Gene: CBR3
Variant: c.730G>A
(p.Val244Met)
rsID: rs1056892
Ref Allele: G
Alt Allele: A
Freq: 39.35%
CADD: 18.79

ClinVar Submissions (1)

- anthracyclines and related substances response - Toxicity/ADR

  ### anthracyclines and related substances response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 11, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 21:36146408

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- UniProt
- OpenSNP
- PubMed (8)

Hetero

GA

Gene: HTR2C
Variant: c.551-3008C>G
rsID: rs1414334
Ref Allele: C
Alt Allele: G
Freq: 76.7066%

ClinVar Submissions (2)

- antipsychotics response - Toxicity/ADR

  ### antipsychotics response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 09, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: X:114903581

- clozapine response - Toxicity/ADR

  ### clozapine response - Toxicity/ADR

  Clozapine is one of the most effective antipsychotics available in the treatment of schizophrenia and the only antipsychotic found to be effective in treatment-resistant schizophrenia. Clozapine is also used to reduce the risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder. Compared to typical antipsychotics, clozapine is far less likely to cause movement disorders, known as extrapyramidal side effects, which include dystonia, akathisia, parkinsonism, and tardive dyskinesia. However, there are significant risks associated with clozapine therapy that limits its use to only the most severely ill patients who have not responded adequately to standard drug therapy. Most notably, because of the risk of clozapine-induced agranulocytosis, clozapine treatment requires monitoring of white blood counts and absolute neutrophil counts, and in the US, the FDA requires that patients receiving clozapine be enrolled in a computer-based registry. Clozapine is metabolized in the liver by the cytochrome P450 (CYP) system of enzymes. CYP1A2 is the main CYP isoform in clozapine metabolism and CYP1A2 activity is an important determinant of clozapine dose. Other CYP enzymes involved in clozapine metabolism include CYP2D6 and CYP3A4. Approximately 6-10% of Caucasians have reduced activity of CYP2D6 ("poor metabolizers"). These individuals may develop higher than expected plasma concentrations of clozapine with usual doses. The FDA-approved drug label for clozapine states that a dose reduction may be necessary in patients who are CYP2D6 poor metabolizers.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 09, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: X:114903581

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 09, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: X:114903581

- olanzapine response - Toxicity/ADR

  ### olanzapine response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 09, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: X:114903581

- risperidone response - Toxicity/ADR

  ### risperidone response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 09, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: X:114903581

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (19)

Homo

GG

Gene: C8orf34
Variant: c.736+8162C>G
rsID: rs1517114
Ref Allele: C
Alt Allele: G
Freq: 62.6147%
CADD: 0.335

ClinVar Submissions (1)

- irinotecan response - Toxicity/ADR

  ### irinotecan response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 11, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 8:68476982

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (4)

Hetero

CG

Gene: ABCC4
Variant: c.3348G>A
(p.Lys1116=)
rsID: rs1751034
Ref Allele: C
Alt Allele: T
Freq: 78.5089%
CADD: 7.895

ClinVar Submissions (1)

- tenofovir response - Metabolism/PK

  ### tenofovir response - Metabolism/PK

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 15, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 13:95062722

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (13)

Homo

TT

Gene: ANKK1;DRD2
Variant: c.2137G>A
(p.Glu713Lys)
rsID: rs1800497
Ref Allele: G
Alt Allele: A
Freq: 27.1009%
CADD: 7.728

ClinVar Submissions (3)

- Dopamine receptor d2, reduced brain density of

  ### Dopamine receptor d2, reduced brain density of

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 24, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 11:113400106
  OMIM Allelic Variant: 608774.0001

- antipsychotics response - Toxicity/ADR

  ### antipsychotics response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 24, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 11:113400106
  OMIM Allelic Variant: 608774.0001

- bupropion response - Efficacy

  ### bupropion response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 24, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 11:113400106
  OMIM Allelic Variant: 608774.0001

- clozapine response - Toxicity/ADR

  ### clozapine response - Toxicity/ADR

  Clozapine is one of the most effective antipsychotics available in the treatment of schizophrenia and the only antipsychotic found to be effective in treatment-resistant schizophrenia. Clozapine is also used to reduce the risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder. Compared to typical antipsychotics, clozapine is far less likely to cause movement disorders, known as extrapyramidal side effects, which include dystonia, akathisia, parkinsonism, and tardive dyskinesia. However, there are significant risks associated with clozapine therapy that limits its use to only the most severely ill patients who have not responded adequately to standard drug therapy. Most notably, because of the risk of clozapine-induced agranulocytosis, clozapine treatment requires monitoring of white blood counts and absolute neutrophil counts, and in the US, the FDA requires that patients receiving clozapine be enrolled in a computer-based registry. Clozapine is metabolized in the liver by the cytochrome P450 (CYP) system of enzymes. CYP1A2 is the main CYP isoform in clozapine metabolism and CYP1A2 activity is an important determinant of clozapine dose. Other CYP enzymes involved in clozapine metabolism include CYP2D6 and CYP3A4. Approximately 6-10% of Caucasians have reduced activity of CYP2D6 ("poor metabolizers"). These individuals may develop higher than expected plasma concentrations of clozapine with usual doses. The FDA-approved drug label for clozapine states that a dose reduction may be necessary in patients who are CYP2D6 poor metabolizers.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 24, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 11:113400106
  OMIM Allelic Variant: 608774.0001

- ethanol response - Toxicity/ADR

  ### ethanol response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 24, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 11:113400106
  OMIM Allelic Variant: 608774.0001

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 24, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 11:113400106
  OMIM Allelic Variant: 608774.0001

- olanzapine response - Toxicity/ADR

  ### olanzapine response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 24, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 11:113400106
  OMIM Allelic Variant: 608774.0001

- risperidone response - Toxicity/ADR

  ### risperidone response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 24, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 11:113400106
  OMIM Allelic Variant: 608774.0001

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- UniProt
- OpenSNP
- PubMed (253)

Hetero

GA

Gene: NQO1
Variant: c.559C>T
(p.Pro187Ser)
rsID: rs1800566
Ref Allele: G
Alt Allele: A
Freq: 22.3528%
CADD: 24.8

ClinVar Submissions (3)

- Alkylating Agents, anthracyclines and related substances, fluorouracil, and Platinum compounds response - Efficacy

  ### Alkylating Agents, anthracyclines and related substances, fluorouracil, and Platinum compounds response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 10, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 16:69711242
  OMIM Allelic Variant: 125860.0001

- Benzene toxicity, susceptibility to

  ### Benzene toxicity, susceptibility to

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 10, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 16:69711242
  OMIM Allelic Variant: 125860.0001

- Breast cancer, post-chemotherapy poor survival in

  ### Breast cancer, post-chemotherapy poor survival in

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 10, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 16:69711242
  OMIM Allelic Variant: 125860.0001

- Leukemia, post-chemotherapy, susceptibility to

  ### Leukemia, post-chemotherapy, susceptibility to

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 10, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 16:69711242
  OMIM Allelic Variant: 125860.0001

- Lung cancer, Autosomal recessive

  ### Lung cancer

  Lung cancer is the leading cause of cancer deaths in the U.S. and worldwide. The 2 major forms of lung cancer are nonsmall cell lung cancer and small cell lung cancer (see 182280), which account for 85% and 15% of all lung cancers, respectively. Nonsmall cell lung cancer can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. Cigarette smoking causes all types of lung cancer, but it is most strongly linked with small cell lung cancer and squamous cell carcinoma. Adenocarcinoma is the most common type in patients who have never smoked. Nonsmall cell lung cancer is often diagnosed at an advanced stage and has a poor prognosis (summary by Herbst et al., 2008).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 10, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 16:69711242
  OMIM Allelic Variant: 125860.0001

Expert Reviewed Clinically Significant drug response

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (135)

Homo

AA

Gene: FCGR2A
Variant: c.497A>G
(p.His166Arg)
rsID: rs1801274
Ref Allele: A
Alt Allele: G
Freq: 50.5431%
CADD: 0.08

ClinVar Submissions (3)

- Lupus nephritis, susceptibility to

  ### Lupus nephritis, susceptibility to

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 28, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 1:161509955
  OMIM Allelic Variant: 146790.0001

- Malaria, severe, susceptibility to

  ### Malaria, severe, susceptibility to

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 28, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 1:161509955
  OMIM Allelic Variant: 146790.0001

- Pseudomonas aeruginosa, susceptibility to chronic infection by, in cystic fibrosis

  ### Pseudomonas aeruginosa, susceptibility to chronic infection by, in cystic fibrosis

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 28, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 1:161509955
  OMIM Allelic Variant: 146790.0001

- not specified

  ### not specified

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 28, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 1:161509955
  OMIM Allelic Variant: 146790.0001

- trastuzumab response - Efficacy

  ### trastuzumab response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 28, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 1:161509955
  OMIM Allelic Variant: 146790.0001

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (132)

Hetero

AG

Gene: MTRR
Variant: c.66A>G
(p.Ile22Met)
rsID: rs1801394
Ref Allele: A
Alt Allele: G
Freq: 43.3765%
CADD: 20.7

ClinVar Submissions (6)

- Disorders of Intracellular Cobalamin Metabolism

  ### Disorders of Intracellular Cobalamin Metabolism

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 30, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 6
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 5:7870860
  OMIM Allelic Variant: 602568.0003

- Down syndrome, susceptibility to

  ### Down syndrome, susceptibility to

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 30, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 6
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 5:7870860
  OMIM Allelic Variant: 602568.0003

- Gastrointestinal stroma tumor

  ### Gastrointestinal stroma tumor

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 30, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 6
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 5:7870860
  OMIM Allelic Variant: 602568.0003

- Neural tube defects, folate-sensitive, susceptibility to

  ### Neural tube defects, folate-sensitive, susceptibility to

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 30, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 6
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 5:7870860
  OMIM Allelic Variant: 602568.0003

- methotrexate response - Toxicity/ADR

  ### methotrexate response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 30, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 6
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 5:7870860
  OMIM Allelic Variant: 602568.0003

- not specified

  ### not specified

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 30, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 6
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 5:7870860
  OMIM Allelic Variant: 602568.0003

Low clinical importance, Likely pathogenic — This common variant (HapMap allele frequency of 31.3%) in a protein involved in folate (B9) and cobalamin (B12) metabolism and is often reported as "MTRR I22M" (an alternative transcript position). Mothers homozygous for this variant are associated with having around a increased chance of a child with Down syndrome (risk of 0.4%, average risk in population is 0.25%). Notably, age plays a far larger role in the rate of Down syndrome (risk is 4.5% for a mother 45-years-of-age), and it is unknown how this variant may combine with the effect of age. There are conflicting reports associating this variant with incidence of neural tube defects, possibly when combined with MTHFR A222V.

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (124)

Homo

GG

Gene: CRHR1
Variant: c.1194+111C>T
rsID: rs1876828
Ref Allele: C
Alt Allele: T
Freq: 14.7992%
CADD: 6.162

ClinVar Submissions (1)

- budesonide response - Efficacy

  ### budesonide response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 07, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 17:45834159

- corticosteroids response - Efficacy

  ### corticosteroids response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 07, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 17:45834159

- fluticasone propionate response - Efficacy

  ### fluticasone propionate response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 07, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 17:45834159

- fluticasone/salmeterol response - Efficacy

  ### fluticasone/salmeterol response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 07, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 17:45834159

- triamcinolone response - Efficacy

  ### triamcinolone response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 07, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 17:45834159

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (35)

Hetero

CT

Gene: ABCB1
Variant: c.2677T>G
(p.Ser893Ala)
rsID: rs2032582
Ref Allele: A
Alt Allele: C
Freq: 67.0951%
CADD: 13.16

ClinVar Submissions (3)

- Inflammatory bowel disease 13

  ### Inflammatory bowel disease 13

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 11, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 7:87531302
  OMIM Allelic Variant: 171050.0003

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 11, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 7:87531302
  OMIM Allelic Variant: 171050.0003

- ondansetron response - Efficacy

  ### ondansetron response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 11, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 7:87531302
  OMIM Allelic Variant: 171050.0003

- simvastatin response - Efficacy

  ### simvastatin response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 11, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 7:87531302
  OMIM Allelic Variant: 171050.0003

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (262)

Homo

CC

Gene: CYP4F2
Variant: c.1297G>A
(p.Val433Met)
rsID: rs2108622
Ref Allele: C
Alt Allele: T
Freq: 22.5551%
CADD: 24.8

ClinVar Submissions (1)

- acenocoumarol response - Dosage

  ### acenocoumarol response - Dosage

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 06, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 19:15879621

- phenprocoumon response - Dosage

  ### phenprocoumon response - Dosage

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 06, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 19:15879621

- warfarin response - Dosage

  ### warfarin response - Dosage

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 06, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 19:15879621

- warfarin response - Other

  ### warfarin response - Other

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 06, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 19:15879621

Insufficiently evaluated pharmacogenetic — Requires 1mg/day greater dose of warfarin.

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- UniProt
- OpenSNP
- PubMed (186)

Homo

TT

Gene: TMEM43;XPC
Variant: c.2815C>A
(p.Gln939Lys)
rsID: rs2228001
Ref Allele: G
Alt Allele: T
Freq: 64.307%
CADD: 14.73

ClinVar Submissions (4)

- Arrhythmogenic right ventricular cardiomyopathy

  ### Arrhythmogenic right ventricular cardiomyopathy

  Arrhythmogenic right ventricular cardiomyopathy (ARVC) – previously referred to as arrhythmogenic right ventricular dysplasia (ARVD) – is characterized by progressive fibrofatty replacement of the myocardium that predisposes to ventricular tachycardia and sudden death in young individuals and athletes. It primarily affects the right ventricle, and it may also involve the left ventricle. The presentation of disease is highly variable even within families, and some affected individuals may not meet established clinical criteria. The mean age at diagnosis is 31 years (±13; range: 4-64 years).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 03, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 4
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 3:14145949

- Xeroderma pigmentosum

  ### Xeroderma pigmentosum

  Xeroderma pigmentosum (XP) is characterized by: Sun sensitivity (severe sunburn with blistering, persistent erythema on minimal sun exposure in ~60% of affected individuals), with marked freckle-like pigmentation of the face before age two years in most affected individuals; Sunlight-induced ocular involvement (photophobia, keratitis, atrophy of the skin of the lids); Greatly increased risk of sunlight-induced cutaneous neoplasms (basal cell carcinoma, squamous cell carcinoma, melanoma). Approximately 25% of affected individuals have neurologic manifestations (acquired microcephaly, diminished or absent deep tendon stretch reflexes, progressive sensorineural hearing loss, and progressive cognitive impairment). The most common causes of death are skin cancer, neurologic degeneration, and internal cancer. The median age at death in persons with XP with neurodegeneration (29 years) was found to be younger than that in persons with XP without neurodegeneration (37 years).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 03, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 4
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 3:14145949

- cisplatin response - Toxicity/ADR

  ### cisplatin response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 03, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 4
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 3:14145949

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 03, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 4
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 3:14145949

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- UniProt
- OpenSNP
- PubMed (79)

Hetero

GT

Gene: VDR
Variant: c.2T>C
(p.Met1Thr)
rsID: rs2228570
Ref Allele: A
Alt Allele: G
Freq: 65.9746%
CADD: 24.6

ClinVar Submissions (3)

- Vitamin D-Dependent Rickets

  ### Vitamin D-Dependent Rickets

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 01, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 12:47879112

- not specified

  ### not specified

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 01, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 12:47879112

- peginterferon alfa-2b and ribavirin response - Efficacy

  ### peginterferon alfa-2b and ribavirin response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 01, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 12:47879112

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (312)

Hetero

AG

Gene: HAS3
Variant: c.279A>G
(p.Ala93=)
rsID: rs2232228
Ref Allele: A
Alt Allele: G
Freq: 33.7801%
CADD: 13.71

ClinVar Submissions (1)

- anthracyclines and related substances response - Toxicity/ADR

  ### anthracyclines and related substances response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 11, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 16:69109674

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (5)

Hetero

AG

Gene: EPHX1
Variant: c.416A>G
(p.His139Arg)
rsID: rs2234922
Ref Allele: A
Alt Allele: G
Freq: 22.966%
CADD: 7.774

ClinVar Submissions (2)

- EPOXIDE HYDROLASE 1 POLYMORPHISM

  ### EPOXIDE HYDROLASE 1 POLYMORPHISM

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 20, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 1:225838705
  OMIM Allelic Variant: 132810.0002

- carbamazepine response - Dosage

  ### carbamazepine response - Dosage

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 20, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 1:225838705
  OMIM Allelic Variant: 132810.0002

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- UniProt
- OpenSNP
- PubMed (79)

Hetero

AG

Gene: CYP2B6
Variant: c.823-197T>C
rsID: rs2279345
Ref Allele: T
Alt Allele: C
Freq: 67.6653%
CADD: 1.711

ClinVar Submissions (1)

- efavirenz response - Metabolism/PK

  ### efavirenz response - Metabolism/PK

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 20, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 19:41009797

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (14)

Hetero

TC

Gene: FDPS
Variant: c.-1-98T>G
rsID: rs2297480
Ref Allele: T
Alt Allele: G
Freq: 30.5492%
CADD: 4.553

ClinVar Submissions (1)

- Bisphosphonates response - Efficacy

  ### Bisphosphonates response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 22, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 1:155309691

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (14)

Hetero

TG

Gene: ADORA2A
Variant: c.-275+1797C>T
rsID: rs2298383
Ref Allele: C
Alt Allele: T
Freq: 47.8283%
CADD: 0.205

ClinVar Submissions (1)

- caffeine response - Toxicity/ADR

  ### caffeine response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 20, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 22:24429543

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (20)

Homo

TT

Gene: VKORC1
Variant: c.283+837T>C
rsID: rs2359612
Ref Allele: A
Alt Allele: G
Freq: 62.7994%
CADD: 0.93

ClinVar Submissions (1)

- warfarin response - Dosage

  ### warfarin response - Dosage

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 07, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 16:31092475

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (49)

Hetero

AG

Gene: CYP3A4
Variant: c.-392G>A
rsID: rs2740574
Ref Allele: C
Alt Allele: T
Freq: 77.7308%
CADD: 3.399

ClinVar Submissions (2)

- CYP3A4 PROMOTER POLYMORPHISM

  ### CYP3A4 PROMOTER POLYMORPHISM

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 23, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 7:99784473
  OMIM Allelic Variant: 124010.0001

- Cyp3a4-v

  ### Cyp3a4-v

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 23, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 7:99784473
  OMIM Allelic Variant: 124010.0001

- tacrolimus response - Dosage

  ### tacrolimus response - Dosage

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 23, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 7:99784473
  OMIM Allelic Variant: 124010.0001

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (110)

Homo

TT

Gene: VKORC1
Variant: c.173+324T>G
rsID: rs2884737
Ref Allele: A
Alt Allele: C
Freq: 16.7232%
CADD: 3.96

ClinVar Submissions (1)

- warfarin response - Dosage

  ### warfarin response - Dosage

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 11, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 16:31094233

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (25)

Hetero

AC

Gene: ERCC1
Variant: c.*197G>T
rsID: rs3212986
Ref Allele: C
Alt Allele: A
Freq: 27.718%
CADD: 0.61

ClinVar Submissions (1)

- Platinum compounds response - Toxicity/ADR

  ### Platinum compounds response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 27, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 19:45409478

- cisplatin response - Toxicity/ADR

  ### cisplatin response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 27, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 19:45409478

- platinum response - Toxicity/ADR

  ### platinum response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 27, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 19:45409478

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (88)

Hetero

CA

Gene: PTGFR
Variant: c.-562T>C
rsID: rs3753380
Ref Allele: T
Alt Allele: C
Freq: 78.9891%
CADD: 6.726

ClinVar Submissions (1)

- latanoprost response - Efficacy

  ### latanoprost response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 21, 2015
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 1:78490747

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (11)

Hetero

TC

Gene: SCN1A
Variant: c.603-91G>A
rsID: rs3812718
Ref Allele: C
Alt Allele: T
Freq: 47.6706%
CADD: 18.66

ClinVar Submissions (2)

- Febrile seizures, familial, 3a

  ### Febrile seizures, familial, 3a

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 23, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 2:166053034
  OMIM Allelic Variant: 182389.0016

- antiepileptics response - Efficacy

  ### antiepileptics response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 23, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 2:166053034
  OMIM Allelic Variant: 182389.0016

- carbamazepine response - Dosage

  ### carbamazepine response - Dosage

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 23, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 2:166053034
  OMIM Allelic Variant: 182389.0016

- carbamazepine response - Efficacy

  ### carbamazepine response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 23, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 2:166053034
  OMIM Allelic Variant: 182389.0016

- phenytoin response - Dosage

  ### phenytoin response - Dosage

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 23, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 2:166053034
  OMIM Allelic Variant: 182389.0016

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (42)

Homo

TT

Gene: SLCO1B1
Variant: c.521T>C
(p.Val174Ala)
rsID: rs4149056
Ref Allele: T
Alt Allele: C
Freq: 11.0578%
CADD: 25.8

ClinVar Submissions (5)

- Rotor syndrome

  ### Rotor syndrome

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 21, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 5
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 12:21178615

- cerivastatin response - Toxicity/ADR

  ### cerivastatin response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 21, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 5
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 12:21178615

- hmg coa reductase inhibitors response - Toxicity/ADR, Metabolism/PK

  ### hmg coa reductase inhibitors response - Toxicity/ADR, Metabolism/PK

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 21, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 5
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 12:21178615

- not provided

  ### not provided

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 21, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 5
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 12:21178615

- not specified

  ### not specified

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 21, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 5
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 12:21178615

- pravastatin response - Metabolism/PK

  ### pravastatin response - Metabolism/PK

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 21, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 5
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 12:21178615

- rosuvastatin response - Other

  ### rosuvastatin response - Other

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 21, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 5
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 12:21178615

- simvastatin acid response - Metabolism/PK

  ### simvastatin acid response - Metabolism/PK

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 21, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 5
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 12:21178615

- simvastatin response - Toxicity/ADR

  ### simvastatin response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 21, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 5
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 12:21178615

Insufficiently evaluated pharmacogenetic — Increased plasma AUC with repaglinide.

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (174)

Hetero

TC

Gene: EGF
Variant: c.-382A>G
rsID: rs4444903
Ref Allele: A
Alt Allele: G
Freq: 52.4321%
CADD: 8.542

ClinVar Submissions (2)

- Renal Hypomagnesemia, Recessive

  ### Renal Hypomagnesemia, Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 01, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 4:109912954

- cetuximab response - Efficacy

  ### cetuximab response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 01, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 4:109912954

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (61)

Hetero

AG

Gene: COQ2
Variant: c.779-1022C>G
rsID: rs4693075
Ref Allele: G
Alt Allele: C
Freq: 61.6184%
CADD: 1.96

ClinVar Submissions (1)

- atorvastatin response - Toxicity/ADR

  ### atorvastatin response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 14, 2015
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 4:83271015

- hmg coa reductase inhibitors response - Toxicity/ADR

  ### hmg coa reductase inhibitors response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 14, 2015
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 4:83271015

- rosuvastatin response - Toxicity/ADR

  ### rosuvastatin response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 14, 2015
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 4:83271015

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (7)

Hetero

GC

Gene: FKBP5
Variant: c.-20+18122T>C
rsID: rs4713916
Ref Allele: A
Alt Allele: G
Freq: 77.1709%
CADD: 0.798

ClinVar Submissions (1)

- Selective serotonin reuptake inhibitors response - Efficacy

  ### Selective serotonin reuptake inhibitors response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 14, 2015
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 6:35702206

- antidepressants response - Efficacy

  ### antidepressants response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 14, 2015
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 6:35702206

- citalopram response - Efficacy

  ### citalopram response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 14, 2015
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 6:35702206

- fluoxetine response - Efficacy

  ### fluoxetine response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 14, 2015
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 6:35702206

- mirtazapine response - Efficacy

  ### mirtazapine response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 14, 2015
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 6:35702206

- paroxetine response - Efficacy

  ### paroxetine response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 14, 2015
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 6:35702206

- venlafaxine response - Efficacy

  ### venlafaxine response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 14, 2015
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 6:35702206

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (30)

Homo

GG

Gene: CYP2C9
Variant: c.820-6326A>C
rsID: rs4917639
Ref Allele: A
Alt Allele: C
Freq: 18.8209%
CADD: 1.887

ClinVar Submissions (1)

- warfarin response - Dosage

  ### warfarin response - Dosage

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 24, 2015
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 10:94965778

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (18)

Hetero

AC

Gene: DPP6
Variant: c.52-71279T>C
rsID: rs6977820
Ref Allele: T
Alt Allele: C
Freq: 58.4257%
CADD: 6.496

ClinVar Submissions (1)

- antipsychotics response - Toxicity/ADR

  ### antipsychotics response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 11, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 7:154374935

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (3)

Homo

CC

Gene: VKORC1
Variant: g.296C>T
rsID: rs7196161
Ref Allele: G
Alt Allele: A
Freq: 55.4918%
CADD: 1.773

ClinVar Submissions (1)

- warfarin response - Dosage

  ### warfarin response - Dosage

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 11, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 16:31099660

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (11)

Hetero

GA

Gene: ITPA
Variant: c.124+21A>C
rsID: rs7270101
Ref Allele: A
Alt Allele: C
Freq: 9.6896%
CADD: 15

ClinVar Submissions (2)

- Inosine triphosphatase deficiency

  ### Inosine triphosphatase deficiency

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 26, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 20:3213247
  OMIM Allelic Variant: 147520.0002

- azathioprine response - Toxicity/ADR

  ### azathioprine response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 26, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 20:3213247
  OMIM Allelic Variant: 147520.0002

- peginterferon alfa-2b and ribavirin response - Toxicity/ADR

  ### peginterferon alfa-2b and ribavirin response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 26, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 20:3213247
  OMIM Allelic Variant: 147520.0002

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (46)

Hetero

AC

Gene: CRHR2
Variant: c.-166-546T>A
rsID: rs7793837
Ref Allele: A
Alt Allele: T
Freq: 40.9069%
CADD: 2.37

ClinVar Submissions (1)

- salbutamol response - Efficacy

  ### salbutamol response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 05, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 7:30687161

- selective beta-2-adrenoreceptor agonists response - Efficacy

  ### selective beta-2-adrenoreceptor agonists response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 05, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 7:30687161

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (6)

Hetero

AT

Gene: HTR2A
Variant: c.614-2211T>C
rsID: rs7997012
Ref Allele: A
Alt Allele: G
Freq: 71.3279%
CADD: 11.64

ClinVar Submissions (3)

- Major depressive disorder, response to citalopram therapy in

  ### Major depressive disorder, response to citalopram therapy in

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 09, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 13:46837850
  OMIM Allelic Variant: 182135.0003

- Selective serotonin reuptake inhibitors response - Efficacy

  ### Selective serotonin reuptake inhibitors response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 09, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 13:46837850
  OMIM Allelic Variant: 182135.0003

- antidepressants response - Efficacy

  ### antidepressants response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 09, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 13:46837850
  OMIM Allelic Variant: 182135.0003

- citalopram response - Efficacy

  ### citalopram response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 09, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 13:46837850
  OMIM Allelic Variant: 182135.0003

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 09, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 13:46837850
  OMIM Allelic Variant: 182135.0003

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (50)

Homo

GG

Gene: VKORC1
Variant: c.283+124G>C
rsID: rs8050894
Ref Allele: C
Alt Allele: G
Freq: 39.1159%
CADD: 1.82

ClinVar Submissions (2)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 09, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 16:31093188

- warfarin response - Dosage

  ### warfarin response - Dosage

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 09, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 16:31093188

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (44)

Hetero

CG

Gene: IFNL3
Variant: g.39252525T>G
rsID: rs8099917
Ref Allele: T
Alt Allele: G
Freq: 15.2539%
CADD: 15.16

ClinVar Submissions (1)

- interferons, peginterferon alfa-2a, peginterferon alfa-2b, and ribavirin response - Efficacy

  ### interferons, peginterferon alfa-2a, peginterferon alfa-2b, and ribavirin response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 16, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 19:39252525

- peginterferon alfa-2a, peginterferon alfa-2b, ribavirin, and telaprevir response - Efficacy

  ### peginterferon alfa-2a, peginterferon alfa-2b, ribavirin, and telaprevir response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 16, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 19:39252525

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (425)

Hetero

TG

Gene: VKORC1
Variant: c.174-136C>T
rsID: rs9934438
Ref Allele: G
Alt Allele: A
Freq: 33.6352%
CADD: 14.98

ClinVar Submissions (5)

- Vitamin K-Dependent Clotting Factors

  ### Vitamin K-Dependent Clotting Factors

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 05, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 5
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 16:31093557
  OMIM Allelic Variant: 608547.0008

- Warfarin response, Autosomal dominant

  ### Warfarin response

  Warfarin is an oral anti-coagulant used world-wide to treat and prevent thrombotic disorders. While it is highly effective, it has a very narrow therapeutic index making it difficult to dose correctly. Genetic variants in both cytochrome P450-2C9 (CYP2C9) and vitamin K-epoxide reductase complex (VKORC1) enzymes, along with non-genetic factors, are known to affect warfarin dose variability. Patients with specific variants in the gene CYP2C9 (the primary warfarin-metabolizing enzyme), such as CYP2C9*2 and CYP2C9*3, may require a lower dose of warfarin as compared to patients without these variants. Patients with a specific variant in VKORC1 (the target enzyme of warfarin), known as -1639G>A or rs9923231, may require a lower warfarin dose as compared to patients who do not have this variant. The combination of CYP2C9 and VKORC1 genetic variants, along with clinical factors, can put some patients at risk for adverse events such as bleeding. Guidelines regarding the use of pharmacogenomic tests in dosing for warfarin have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 05, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 5
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 16:31093557
  OMIM Allelic Variant: 608547.0008

- acenocoumarol response - Dosage

  ### acenocoumarol response - Dosage

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 05, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 5
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 16:31093557
  OMIM Allelic Variant: 608547.0008

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 05, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 5
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 16:31093557
  OMIM Allelic Variant: 608547.0008

- phenprocoumon response - Dosage

  ### phenprocoumon response - Dosage

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 05, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 5
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 16:31093557
  OMIM Allelic Variant: 608547.0008

- warfarin response - Dosage

  ### warfarin response - Dosage

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 05, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 5
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 16:31093557
  OMIM Allelic Variant: 608547.0008

Insufficiently evaluated pharmacogenetic — gene VKORC1 SNP 1173 C>T is strongly associated with low warfarin dose requirement.

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (127)

Hetero

GA

Gene: LPA
Variant: c.3947+467T>C
rsID: rs10455872
Ref Allele: A
Alt Allele: G
Freq: 4.1762%uncommon
CADD: 0.033

ClinVar Submissions (1)

- hmg coa reductase inhibitors response - Efficacy, Toxicity/ADR

  ### hmg coa reductase inhibitors response - Efficacy, Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 08, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 6:160589086

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (62)

Hetero

AG

Gene: SLCO1B1
Variant: c.1865+4846T>C
rsID: rs11045879
Ref Allele: T
Alt Allele: C
Freq: 18.1639%
CADD: 6.151

ClinVar Submissions (1)

- methotrexate response - Toxicity/ADR

  ### methotrexate response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 20, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 12:21229685

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (17)

Hetero

TC

Gene: C11orf65
Variant: c.175-5285G>T
rsID: rs11212617
Ref Allele: C
Alt Allele: A
Freq: 47.0924%
CADD: 2.33

ClinVar Submissions (1)

- metformin response - Efficacy

  ### metformin response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 17, 2017
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 11:108412434

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (19)

Hetero

CA

Gene: NT5C2
Variant: c.175+1178A>G
rsID: rs11598702
Ref Allele: T
Alt Allele: C
Freq: 30.4114%
CADD: 3.851

ClinVar Submissions (1)

- gemcitabine response - Other

  ### gemcitabine response - Other

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 19, 2015
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 10:103138228

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (9)

Hetero

TC

Gene: IFNL3
Variant: c.259-126T>C
rsID: rs11881222
Ref Allele: A
Alt Allele: G
Freq: 29.6994%
CADD: 4.956

ClinVar Submissions (1)

- peginterferon alfa-2a response - Efficacy

  ### peginterferon alfa-2a response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 19:39244283

- peginterferon alfa-2b response - Efficacy

  ### peginterferon alfa-2b response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 19:39244283

- ribavirin response - Efficacy

  ### ribavirin response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 19:39244283

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (32)

Hetero

AG

Gene: IFNL3;IFNL4
Variant: c.151-152G>A
rsID: rs12979860
Ref Allele: C
Alt Allele: T
Freq: 39.0673%
CADD: 1.703

ClinVar Submissions (2)

- boceprevir response - Efficacy

  ### boceprevir response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 05, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 19:39248147

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 05, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 19:39248147

- peginterferon alfa-2a, peginterferon alfa-2b, and ribavirin response - Efficacy

  ### peginterferon alfa-2a, peginterferon alfa-2b, and ribavirin response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 05, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 19:39248147

- peginterferon alfa-2a, peginterferon alfa-2b, ribavirin, and telaprevir response - Efficacy

  ### peginterferon alfa-2a, peginterferon alfa-2b, ribavirin, and telaprevir response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 05, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 19:39248147

- peginterferon alfa-2b response - Efficacy

  ### peginterferon alfa-2b response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 05, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 19:39248147

- ribavirin response - Efficacy

  ### ribavirin response - Efficacy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 05, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 2
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 19:39248147

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (602)

Hetero

CT

Gene: MC4R
Variant: g.60183864T>C
rsID: rs17782313
Ref Allele: T
Alt Allele: C
Freq: 24.1128%
CADD: 3.5

ClinVar Submissions (1)

- antipsychotics response - Toxicity/ADR

  ### antipsychotics response - Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 22, 2015
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 18:60183864

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (181)

Homo

CC

## "Clinically significant" variants

Below are mutations from ClinVar that were submitted as "clinically significant." Variants shown may or may not be truly clinically significant. The data presented has no guarantees of reporting accuracy. Heterozygous variants are reported as yellow and homozygous variants as red. A red or yellow variant does not necessarily mean one has or carries a condition or disease. This is for research and educational purposes only.

Gene: TERT
Variant: c.604G>A
(p.Ala202Thr)
rsID: rs121918661
Ref Allele: C
Alt Allele: T
Freq: 0.0303%rare
CADD: 1.552

ClinVar Submissions (8)

- Aplastic anemia

  ### Aplastic anemia

  Aplastic anemia is a serious disorder of the bone marrow that affects between 2 and 5 persons per million per year. About 75% of these cases are classified as idiopathic (Young, 2000). In about 15% of cases a drug or infection can be identified that precipitates the aplasia, although why only some individuals are susceptible is unclear. In about 5 to 10% of patients, the aplastic anemia is constitutional--i.e., is familial or presents with one or more associated somatic abnormalities (summary by Vulliamy et al., 2002).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 26, 2019
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 8
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 5:1294282
  OMIM Allelic Variant: 187270.0001

- Dyskeratosis congenita, autosomal dominant, 2, Autosomal dominant

  ### Dyskeratosis congenita, autosomal dominant, 2

  Dyskeratosis congenita (DC), a telomere biology disorder, is characterized by a classic triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia. The classic triad may not be present in all individuals. People with DC are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML), solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include: abnormal pigmentation changes not restricted to the upper chest and neck, eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), and dental abnormalities (caries, periodontal disease, taurodauntism). Although most persons with DC have normal psychomotor development and normal neurologic function, significant developmental delay is present in the two variants in which additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome). Onset and progression of manifestations of DC vary: at the mild end of the spectrum are those who have only minimal physical findings with normal bone marrow function, and at the severe end are those who have the diagnostic triad and early-onset BMF.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 26, 2019
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 8
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 5:1294282
  OMIM Allelic Variant: 187270.0001

- Dyskeratosis congenita, autosomal dominant, 2, Autosomal dominant

  ### Dyskeratosis congenita, autosomal dominant, 2

  Dyskeratosis congenita (DC), a telomere biology disorder, is characterized by a classic triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia. The classic triad may not be present in all individuals. People with DC are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML), solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include: abnormal pigmentation changes not restricted to the upper chest and neck, eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), and dental abnormalities (caries, periodontal disease, taurodauntism). Although most persons with DC have normal psychomotor development and normal neurologic function, significant developmental delay is present in the two variants in which additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome). Onset and progression of manifestations of DC vary: at the mild end of the spectrum are those who have only minimal physical findings with normal bone marrow function, and at the severe end are those who have the diagnostic triad and early-onset BMF.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 26, 2019
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 8
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 5:1294282
  OMIM Allelic Variant: 187270.0001

- Idiopathic fibrosing alveolitis, chronic form, Autosomal dominant

  ### Idiopathic fibrosing alveolitis, chronic form

  Familial pulmonary fibrosis (FPF in this GeneReview) is defined as idiopathic interstitial pneumonia (IIP) in two or more first-degree relatives (parent, sib, or offspring). Up to 20% of cases of IIP cluster in families. The clinical findings of IIP are bibasilar reticular abnormalities, ground glass opacities, or diffuse nodular lesions on high-resolution computed tomography and abnormal pulmonary function studies that include evidence of restriction (reduced VC with an increase in FEV1/FVC ratio) and/or impaired gas exchange (increased P(A-a)O2 with rest or exercise or decreased diffusion capacity of the lung for carbon monoxide [DLCO]). FPF usually presents between ages 50 and 70 years. FPF may be complicated by lung cancer; bronchoalveolar cell carcinoma, small-cell carcinoma, and adenocarcinoma have been described.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 26, 2019
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 8
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 5:1294282
  OMIM Allelic Variant: 187270.0001

- Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1, Autosomal dominant

  ### Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1

  Shortened telomeres can cause a wide variety of clinical features that constitute a phenotypic spectrum. The most severe form is dyskeratosis congenita (see, e.g., 127750), characterized by early childhood onset of skin abnormalities, bone marrow failure, predisposition to malignancy, and risk of pulmonary and hepatic fibrosis. Adult-onset pulmonary fibrosis is the most common manifestation of mutant telomerase genes. Other manifestations include aplastic anemia due to bone marrow failure, hepatic fibrosis, and increased cancer risk, particularly myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Phenotype, age at onset, and severity are determined by telomere length, not just telomerase mutation (summary by Armanios, 2009). The genetic diagnosis of telomere-related bone marrow failure and pulmonary fibrosis has implications for treatment because affected individuals generally do not respond to immunosuppression and may be at increased risk for fatal complications after bone marrow or lung transplantation (Parry et al., 2011). Genetic Heterogeneity of Telomere-Related Pulmonary Fibrosis and/or Bone Marrow Failure Also see PFBMFT2 (614743), caused by mutation in the TERC gene (602322) on chromosome 3q26; PFBMFT3 (616373), caused by mutation in the RTEL1 gene (608833) on chromosome 20q13; and PFBMFT4 (616371), caused by mutation in the PARN gene (604212) on chromosome 16p13.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 26, 2019
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 8
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 5:1294282
  OMIM Allelic Variant: 187270.0001

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 26, 2019
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 8
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 5:1294282
  OMIM Allelic Variant: 187270.0001

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 26, 2019
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 8
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 5:1294282
  OMIM Allelic Variant: 187270.0001

Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (3)

Hetero

CT

Gene: CPA6
Variant: c.619C>G
(p.Gln207Glu)
rsID: rs35993949
Ref Allele: G
Alt Allele: C
Freq: 0.1354%rare
CADD: 26.7

ClinVar Submissions (7)

- Epilepsy, familial temporal lobe, 5, Autosomal dominant

  ### Epilepsy, familial temporal lobe, 5

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 25, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 7
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 8:67506804
  OMIM Allelic Variant: 609562.0003

- Febrile seizures, familial, 11, Autosomal recessive

  ### Febrile seizures, familial, 11

  Familial febrile seizures-11 is an autosomal recessive seizure disorder characterized by early childhood onset of simple or complex seizures associated with fever. These seizures usually remit later in childhood with no neurologic sequelae (summary by Salzmann et al., 2012). For a general description and a discussion of genetic heterogeneity of familial febrile seizures, see FEB1 (121210).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 25, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 7
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 8:67506804
  OMIM Allelic Variant: 609562.0003

- Global developmental delay

  ### Global developmental delay

  A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age. [DDD:hvfirth, HPO:sdoelken]

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 25, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 7
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 8:67506804
  OMIM Allelic Variant: 609562.0003

- Rolandic epilepsy

  ### Rolandic epilepsy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 25, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 7
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 8:67506804
  OMIM Allelic Variant: 609562.0003

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 25, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 7
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 8:67506804
  OMIM Allelic Variant: 609562.0003

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 25, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 7
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 8:67506804
  OMIM Allelic Variant: 609562.0003

Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (2)

Hetero

GC

Gene: SERPINA6
Variant: c.344T>A
(p.Leu115His)
rsID: rs113418909
Ref Allele: A
Alt Allele: T
Freq: 0.2357%rare
CADD: 24.7

ClinVar Submissions (2)

- Corticosteroid-binding globulin deficiency, Autosomal dominant

  ### Corticosteroid-binding globulin deficiency

  Corticosteroid-binding globulin deficiency is a condition with subtle signs and symptoms, the most frequent being extreme tiredness (fatigue), especially after physical exertion. Many people with this condition have unusually low blood pressure (hypotension). Some affected individuals have a fatty liver or experience chronic pain, particularly in their muscles. These features vary among affected individuals, even those within the same family.Many people with corticosteroid-binding globulin deficiency have only one or two of these features; others have no signs and symptoms of the disorder and are only diagnosed after a relative is found to be affected.Some people with corticosteroid-binding globulin deficiency also have a condition called chronic fatigue syndrome. The features of chronic fatigue syndrome are prolonged fatigue that interferes with daily activities, as well as general symptoms, such as sore throat or headaches.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 08, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 2
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 14:94314305
  OMIM Allelic Variant: 122500.0001

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 08, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 2
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 14:94314305
  OMIM Allelic Variant: 122500.0001

Moderate clinical importance, Uncertain pathogenic — Reported to cause corticosteroid deficiency in a recessive fashion, a disease which can cause fatigue after exertion. This variant was reported by Van Baelen et al 1982 (PMID: 7061486), and recorded in ClinVar by OMIM (http://www.ncbi.nlm.nih.gov/clinvar/RCV000018495/). Van Baelen et al described this variant as "transcortin Leuven", who reported the variant protein product had 3.6-fold reduced affinity for cortisol at 28C.

Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (2)

Hetero

AT

Gene: ATP8B1
Variant: c.208G>A
(p.Asp70Asn)
rsID: rs34719006
Ref Allele: C
Alt Allele: T
Freq: 0.2572%rare
CADD: 23.7

ClinVar Submissions (4)

- Cholestasis of pregnancy, Autosomal dominant

  ### Cholestasis of pregnancy

  Intrahepatic cholestasis of pregnancy is a reversible form of cholestasis that occurs most often in the third trimester of pregnancy and recurs in 45 to 70% of subsequent pregnancies. Symptoms include pruritus, jaundice, increased serum bile salts, and abnormal liver enzymes, all of which resolve rapidly after delivery. However, the condition is associated with fetal complications, including placental insufficiency, premature labor, fetal distress, and intrauterine death. Some women with ICP may also be susceptible to oral contraceptive-induced cholestasis (OCIC) (summary by Pasmant et al., 2012). Genetic Heterogeneity of Intrahepatic Cholestasis of Pregnancy See also ICP3 (614972), caused by mutation in the ABCB4 gene (171060).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 05, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 4
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 18:57706561
  OMIM Allelic Variant: 602397.0010

- Cholestasis, benign recurrent intrahepatic 1

  ### Cholestasis, benign recurrent intrahepatic 1

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 05, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 4
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 18:57706561
  OMIM Allelic Variant: 602397.0010

- Progressive familial intrahepatic cholestasis 2, Autosomal recessive

  ### Progressive familial intrahepatic cholestasis 2

  ATP8B1 deficiency encompasses a phenotypic spectrum ranging from severe to intermediate to mild, based on an individual's clinical findings and laboratory test results, including liver biopsy. Severe ATP8B1 deficiency is characterized by onset of symptoms of cholestasis (pruritus and attacks of jaundice) within the first few months of life. Secondary manifestations such as coagulopathy (due to vitamin K deficiency), malabsorption, and poor weight gain may present earlier than age three months. Without surgical intervention, cirrhosis and evolution to end-stage hepatic failure and death usually ensue before the third decade. Mild ATP8B1 deficiency is characterized by intermittent episodes of cholestasis manifest as severe pruritus and jaundice; chronic liver damage does not typically develop. In contrast to patients in whom bouts of cholestasis are induced only by particular triggers known to increase risk of cholestasis (drug exposure, shifts in hormonal milieu [including those resulting from ingestion of contraceptive drugs or from pregnancy], coexistent malignancy), some or all bouts of cholestasis in individuals with mild ATP8B1 deficiency have different or unknown triggers.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 05, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 4
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 18:57706561
  OMIM Allelic Variant: 602397.0010

- Progressive intrahepatic cholestasis, Autosomal recessive

  ### Progressive intrahepatic cholestasis

  ATP8B1 deficiency encompasses a phenotypic spectrum ranging from severe to intermediate to mild, based on an individual's clinical findings and laboratory test results, including liver biopsy. Severe ATP8B1 deficiency is characterized by onset of symptoms of cholestasis (pruritus and attacks of jaundice) within the first few months of life. Secondary manifestations such as coagulopathy (due to vitamin K deficiency), malabsorption, and poor weight gain may present earlier than age three months. Without surgical intervention, cirrhosis and evolution to end-stage hepatic failure and death usually ensue before the third decade. Mild ATP8B1 deficiency is characterized by intermittent episodes of cholestasis manifest as severe pruritus and jaundice; chronic liver damage does not typically develop. In contrast to patients in whom bouts of cholestasis are induced only by particular triggers known to increase risk of cholestasis (drug exposure, shifts in hormonal milieu [including those resulting from ingestion of contraceptive drugs or from pregnancy], coexistent malignancy), some or all bouts of cholestasis in individuals with mild ATP8B1 deficiency have different or unknown triggers.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 05, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 4
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 18:57706561
  OMIM Allelic Variant: 602397.0010

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 05, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 4
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 18:57706561
  OMIM Allelic Variant: 602397.0010

Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (2)

Hetero

CT

Gene: ABCA4
Variant: c.5882G>A
(p.Gly1961Glu)
rsID: rs1800553
Ref Allele: C
Alt Allele: T
Freq: 0.2692%rare
CADD: 26.5

ClinVar Submissions (17)

- ABCA4-Related Disorders

  ### ABCA4-Related Disorders

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 04, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 17
  Clinical Significance: Pathogenic/Likely pathogenic, risk factor
  Assembly: GRCh38
  Chromosome/Position: 1:94008251
  OMIM Allelic Variant: 601691.0007

- Age-related macular degeneration 2, Autosomal dominant

  ### Age-related macular degeneration 2

  Age-related macular degeneration is an eye disease that is a leading cause of vision loss in older people in developed countries. The vision loss usually becomes noticeable in a person's sixties or seventies and tends to worsen over time.Age-related macular degeneration mainly affects central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces. The vision loss in this condition results from a gradual deterioration of light-sensing cells in the tissue at the back of the eye that detects light and color (the retina). Specifically, age-related macular degeneration affects a small area near the center of the retina, called the macula, which is responsible for central vision. Side (peripheral) vision and night vision are generally not affected, but reduced dim light (scotopic) vision often occurs in the early stages of the disease.Researchers have described two major types of age-related macular degeneration, known as the dry form and the wet form. The dry form is much more common, accounting for 85 to 90 percent of all cases of age-related macular degeneration. It is characterized by a buildup of yellowish deposits called drusen beneath the retina and vision loss that worsens slowly over time. The condition typically affects vision in both eyes, although vision loss often occurs in one eye before the other.The wet form of age-related macular degeneration is associated with severe vision loss that can worsen rapidly. This form of the condition is characterized by the growth of abnormal, fragile blood vessels underneath the macula. These vessels leak blood and fluid, which damages the macula and makes central vision appear blurry and distorted.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 04, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 17
  Clinical Significance: Pathogenic/Likely pathogenic, risk factor
  Assembly: GRCh38
  Chromosome/Position: 1:94008251
  OMIM Allelic Variant: 601691.0007

- Cone-rod dystrophy 3

  ### Cone-rod dystrophy 3

  Cone-rod dystrophy is a group of related eye disorders that causes vision loss, which becomes more severe over time. These disorders affect the retina, which is the layer of light-sensitive tissue at the back of the eye. In people with cone-rod dystrophy, vision loss occurs as the light-sensing cells of the retina gradually deteriorate.The first signs and symptoms of cone-rod dystrophy, which often occur in childhood, are usually decreased sharpness of vision (visual acuity) and increased sensitivity to light (photophobia). These features are typically followed by impaired color vision (dyschromatopsia), blind spots (scotomas) in the center of the visual field, and partial side (peripheral) vision loss. Over time, affected individuals develop night blindness and a worsening of their peripheral vision, which can limit independent mobility. Decreasing visual acuity makes reading increasingly difficult and most affected individuals are legally blind by mid-adulthood. As the condition progresses, individuals may develop involuntary eye movements (nystagmus).There are more than 30 types of cone-rod dystrophy, which are distinguished by their genetic cause and their pattern of inheritance: autosomal recessive, autosomal dominant, and X-linked. Additionally, cone-rod dystrophy can occur alone without any other signs and symptoms or it can occur as part of a syndrome that affects multiple parts of the body.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 04, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 17
  Clinical Significance: Pathogenic/Likely pathogenic, risk factor
  Assembly: GRCh38
  Chromosome/Position: 1:94008251
  OMIM Allelic Variant: 601691.0007

- Inborn genetic diseases

  ### Inborn genetic diseases

  Diseases that are caused by genetic mutations present during embryo or fetal development, although they may be observed later in life. The mutations may be inherited from a parent's genome or they may be acquired in utero.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 04, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 17
  Clinical Significance: Pathogenic/Likely pathogenic, risk factor
  Assembly: GRCh38
  Chromosome/Position: 1:94008251
  OMIM Allelic Variant: 601691.0007

- MACULAR DEGENERATION, AGE-RELATED, 2, SUSCEPTIBILITY TO

  ### MACULAR DEGENERATION, AGE-RELATED, 2, SUSCEPTIBILITY TO

  Macular dystrophy is a nonspecific term for premature retinal cell aging and cell death, generally confied to the macula in which no clear extrinsic cause is evident.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 04, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 17
  Clinical Significance: Pathogenic/Likely pathogenic, risk factor
  Assembly: GRCh38
  Chromosome/Position: 1:94008251
  OMIM Allelic Variant: 601691.0007

- Macular dystrophy

  ### Macular dystrophy

  A group of disorders involving predominantly the posterior portion of the ocular fundus, due to degeneration in the sensory layer of the RETINA; RETINAL PIGMENT EPITHELIUM; BRUCH MEMBRANE; CHOROID; or a combination of these tissues.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 04, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 17
  Clinical Significance: Pathogenic/Likely pathogenic, risk factor
  Assembly: GRCh38
  Chromosome/Position: 1:94008251
  OMIM Allelic Variant: 601691.0007

- Retinal dystrophy

  ### Retinal dystrophy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 04, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 17
  Clinical Significance: Pathogenic/Likely pathogenic, risk factor
  Assembly: GRCh38
  Chromosome/Position: 1:94008251
  OMIM Allelic Variant: 601691.0007

- Stargardt disease 1, Autosomal recessive

  ### Stargardt disease 1

  Stargardt macular degeneration is a genetic eye disorder that causes progressive vision loss. This disorder affects the retina, the specialized light-sensitive tissue that lines the back of the eye. Specifically, Stargardt macular degeneration affects a small area near the center of the retina called the macula. The macula is responsible for sharp central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces. In most people with Stargardt macular degeneration, a fatty yellow pigment (lipofuscin) builds up in cells underlying the macula. Over time, the abnormal accumulation of this substance can damage cells that are critical for clear central vision. In addition to central vision loss, people with Stargardt macular degeneration have problems with night vision that can make it difficult to navigate in low light. Some affected individuals also have impaired color vision. The signs and symptoms of Stargardt macular degeneration typically appear in late childhood to early adulthood and worsen over time.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 04, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 17
  Clinical Significance: Pathogenic/Likely pathogenic, risk factor
  Assembly: GRCh38
  Chromosome/Position: 1:94008251
  OMIM Allelic Variant: 601691.0007

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 04, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 17
  Clinical Significance: Pathogenic/Likely pathogenic, risk factor
  Assembly: GRCh38
  Chromosome/Position: 1:94008251
  OMIM Allelic Variant: 601691.0007

High clinical importance, Likely pathogenic — This rare variant causes Stargardt Disease in a recessive manner. It was hypothesized to increase susceptibility to age-related macular degeneration, but subsequent studies have contradicted this hypothesis.

Clinically Significant Pathogenic/Likely pathogenic, risk factor

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (38)

Hetero

CT

Gene: CPA6
Variant: c.799G>A
(p.Gly267Arg)
rsID: rs61738009
Ref Allele: C
Alt Allele: T
Freq: 0.2811%rare
CADD: 27.1

ClinVar Submissions (6)

- Epilepsy, familial temporal lobe, 5, Autosomal dominant

  ### Epilepsy, familial temporal lobe, 5

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 25, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 6
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 8:67483807
  OMIM Allelic Variant: 609562.0002

- Febrile seizures, familial, 11, Autosomal recessive

  ### Febrile seizures, familial, 11

  Familial febrile seizures-11 is an autosomal recessive seizure disorder characterized by early childhood onset of simple or complex seizures associated with fever. These seizures usually remit later in childhood with no neurologic sequelae (summary by Salzmann et al., 2012). For a general description and a discussion of genetic heterogeneity of familial febrile seizures, see FEB1 (121210).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 25, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 6
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 8:67483807
  OMIM Allelic Variant: 609562.0002

- Global developmental delay

  ### Global developmental delay

  A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age. [DDD:hvfirth, HPO:sdoelken]

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 25, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 6
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 8:67483807
  OMIM Allelic Variant: 609562.0002

- Rolandic epilepsy

  ### Rolandic epilepsy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 25, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 6
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 8:67483807
  OMIM Allelic Variant: 609562.0002

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 25, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 6
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 8:67483807
  OMIM Allelic Variant: 609562.0002

Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (3)

Hetero

CT

Gene: IFIH1
Variant: c.1641+1G>C
rsID: rs35337543
Ref Allele: C
Alt Allele: G
Freq: 0.7972%rare
CADD: 26

ClinVar Submissions (3)

- Aicardi-Goutieres syndrome 7, Autosomal dominant

  ### Aicardi-Goutieres syndrome 7

  Most characteristically, Aicardi-Goutières syndrome (AGS) manifests as an early-onset encephalopathy that usually, but not always, results in severe intellectual and physical disability. A subgroup of infants with AGS present at birth with abnormal neurologic findings, hepatosplenomegaly, elevated liver enzymes, and thrombocytopenia, a picture highly suggestive of congenital infection. Otherwise, most affected infants present at variable times after the first few weeks of life, frequently after a period of apparently normal development. Typically, they demonstrate the subacute onset of a severe encephalopathy characterized by extreme irritability, intermittent sterile pyrexias, loss of skills, and slowing of head growth. Over time, as many as 40% develop chilblain skin lesions on the fingers, toes, and ears. It is becoming apparent that atypical, sometimes milder, cases of AGS exist, and thus the true extent of the phenotype associated with pathogenic variants in the AGS-related genes is not yet known.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 03, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 2:162279995

- Singleton-Merten syndrome 1, Autosomal dominant

  ### Singleton-Merten syndrome 1

  Singleton-Merten syndrome (SGMRT) is an uncommon autosomal dominant disorder characterized by abnormalities of blood vessels, teeth, and bone. Calcifications of the aorta and aortic and mitral valves occur in childhood or puberty and can lead to early death. Dental findings include delayed primary tooth exfoliation and permanent tooth eruption, truncated tooth root formation, early-onset periodontal disease, and severe root and alveolar bone resorption associated with dysregulated mineralization, leading to tooth loss. Osseous features consist of osteoporosis, either generalized or limited to distal extremities, distal limb osteolysis, widened medullary cavities, and easy tearing of tendons from bone. Less common features are mild facial dysmorphism (high anterior hair line, broad forehead, smooth philtrum, thin upper vermilion border), generalized muscle weakness, psoriasis, early-onset glaucoma, and recurrent infections. The disorder manifests with variable inter- and intrafamilial phenotypes (summary by Rutsch et al., 2015). Genetic Heterogeneity of Singleton-Merten Syndrome An atypical form of Singleton-Merten syndrome (SGMRT2; 616298) is caused by mutation in the DDX58 gene (609631) on chromosome 9p21.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 03, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 2:162279995

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 03, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 2:162279995

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 03, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 2:162279995

Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (11)

Hetero

CG

Gene: BLK
Variant: c.211G>A
(p.Ala71Thr)
rsID: rs55758736
Ref Allele: G
Alt Allele: A
Freq: 1.4478%uncommon
CADD: 11.98

ClinVar Submissions (7)

- Maturity onset diabetes mellitus in young, Autosomal dominant

  ### Maturity onset diabetes mellitus in young

  Maturity-onset diabetes of the young is an autosomal dominant form of diabetes typically occurring before 25 years of age and caused by primary insulin secretion defects. Despite its low prevalence, MODY is not a single entity but represents genetic, metabolic, and clinical heterogeneity (Vaxillaire and Froguel, 2008). Genetic Heterogeneity of MODY MODY1 (125850) is caused by heterozygous mutation in the hepatocyte nuclear factor-4-alpha gene (HNF4A; 600281) on chromosome 20. MODY2 (125851) is caused by heterozygous mutation in the glucokinase gene (GCK; 138079) on chromosome 7. MODY3 (600496) is caused by heterozygous mutation in the hepatocyte nuclear factor-1alpha gene (HNF1A; 142410) on chromosome 12q24.2. MODY4 (606392) is caused by heterozygous mutation in the pancreas/duodenum homeobox protein-1 gene (PDX1; 600733) on chromosome 13q12.1. MODY5 (137920) is caused by heterozygous mutation in the gene encoding hepatic transcription factor-2 (TCF2; 189907) on chromosome 17cen-q21.3. MODY6 (606394) is caused by heterozygous mutation in the NEUROD1 gene (601724) on chromosome 2q32. MODY7 (610508) is caused by heterozygous mutation in the KLF11 gene (603301) on chromosome 2p25. MODY8 (609812), or diabetes-pancreatic exocrine dysfunction syndrome, is caused by heterozygous mutation in the CEL gene (114840) on chromosome 9q34. MODY9 (612225) is caused by heterozygous mutation in the PAX4 gene (167413) on chromosome 7q32. MODY10 (613370) is caused by heterozygous mutation in the insulin gene (INS; 176730) on chromosome 11p15.5. MODY11 (613375) is caused by heterozygous mutation in the BLK gene (191305) on chromosome 8p23. MODY13 (616329) is caused by heterozygous mutation in the KCNJ11 gene (600937) on chromosome 11p15. MODY14 (616511) is caused by heterozygous mutation in the APPL1 gene (604299) on chromosome 3p14.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 21, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 7
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 8:11548067
  OMIM Allelic Variant: 191305.0001

- Maturity-onset diabetes of the young, type 11, Autosomal dominant

  ### Maturity-onset diabetes of the young, type 11

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 21, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 7
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 8:11548067
  OMIM Allelic Variant: 191305.0001

- Monogenic diabetes

  ### Monogenic diabetes

  Diabetes mellitus caused by mutation(s) in a single gene, usually presenting in childhood or early adulthood.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 21, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 7
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 8:11548067
  OMIM Allelic Variant: 191305.0001

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 21, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 7
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 8:11548067
  OMIM Allelic Variant: 191305.0001

Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (7)

Hetero

GA

Gene: SEMA4A
Variant: c.2138G>A
(p.Arg713Gln)
rsID: rs41265017
Ref Allele: G
Alt Allele: A
Freq: 3.1266%uncommon
CADD: 22.6

ClinVar Submissions (5)

- Cone-Rod Dystrophy, Recessive

  ### Cone-Rod Dystrophy, Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 5
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 1:156176849
  OMIM Allelic Variant: 607292.0003

- Retinitis Pigmentosa, Recessive

  ### Retinitis Pigmentosa, Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 5
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 1:156176849
  OMIM Allelic Variant: 607292.0003

- Retinitis pigmentosa 35, Autosomal dominant

  ### Retinitis pigmentosa 35

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 5
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 1:156176849
  OMIM Allelic Variant: 607292.0003

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 5
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 1:156176849
  OMIM Allelic Variant: 607292.0003

Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (5)

Hetero

GA

Gene: ADA
Variant: c.22G>A
(p.Asp8Asn)
rsID: rs73598374
Ref Allele: C
Alt Allele: T
Freq: 4.1515%uncommon
CADD: 19.31

ClinVar Submissions (3)

- Adenosine deaminase 2 allozyme

  ### Adenosine deaminase 2 allozyme

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 13, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 20:44651586
  OMIM Allelic Variant: 608958.0021

- Severe combined immunodeficiency due to ADA deficiency

  ### Severe combined immunodeficiency due to ADA deficiency

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 13, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 20:44651586
  OMIM Allelic Variant: 608958.0021

- not specified

  ### not specified

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 13, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 20:44651586
  OMIM Allelic Variant: 608958.0021

Low clinical importance, Likely benign — This common variant is reported to reduce adenosine deaminase enzyme activity. It has been associated with an increased tendency for non-REM sleep -- more slow wave sleep, less nocturnal wakings, and a stronger negative impact of sleep deprivation. A role for this gene and variant was previously proposed for autism susceptibility, but this is controversial and was not replicated by later studies.

Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (10)

Homo

TT

Gene: GAA
Variant: c.2065G>A
(p.Glu689Lys)
rsID: rs1800309
Ref Allele: G
Alt Allele: A
Freq: 4.5426%uncommon
CADD: 18.3

ClinVar Submissions (8)

- Acid alpha-glucosidase, allele 4

  ### Acid alpha-glucosidase, allele 4

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 09, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 8
  Clinical Significance: Conflicting interpretations of pathogenicity, other
  Assembly: GRCh38
  Chromosome/Position: 17:80113242
  OMIM Allelic Variant: 606800.0011

- Glycogen storage disease, type II

  ### Glycogen storage disease, type II

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 09, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 8
  Clinical Significance: Conflicting interpretations of pathogenicity, other
  Assembly: GRCh38
  Chromosome/Position: 17:80113242
  OMIM Allelic Variant: 606800.0011

- not provided

  ### not provided

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 09, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 8
  Clinical Significance: Conflicting interpretations of pathogenicity, other
  Assembly: GRCh38
  Chromosome/Position: 17:80113242
  OMIM Allelic Variant: 606800.0011

- not specified

  ### not specified

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 09, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 8
  Clinical Significance: Conflicting interpretations of pathogenicity, other
  Assembly: GRCh38
  Chromosome/Position: 17:80113242
  OMIM Allelic Variant: 606800.0011

Low clinical importance, Uncertain benign — This is also known as the GAA*4 allozyme is frequent in the Asian population and appears to have somewhat reduced enzyme activity. Kroos et al. rule out pathogenic effect.

Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (5)

Hetero

GA

Gene: MC1R
Variant: c.451C>T
(p.Arg151Cys)
rsID: rs1805007
Ref Allele: C
Alt Allele: T
Freq: 4.701%uncommon
CADD: 25.5

ClinVar Submissions (5)

- Cutaneous malignant melanoma 5

  ### Cutaneous malignant melanoma 5

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 5
  Clinical Significance: Conflicting interpretations of pathogenicity, Affects, association, risk factor
  Assembly: GRCh38
  Chromosome/Position: 16:89919709
  OMIM Allelic Variant: 155555.0004

- Increased analgesia from kappa-opioid receptor agonist, female-specific

  ### Increased analgesia from kappa-opioid receptor agonist, female-specific

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 5
  Clinical Significance: Conflicting interpretations of pathogenicity, Affects, association, risk factor
  Assembly: GRCh38
  Chromosome/Position: 16:89919709
  OMIM Allelic Variant: 155555.0004

- Malignant Melanoma Susceptibility

  ### Malignant Melanoma Susceptibility

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 5
  Clinical Significance: Conflicting interpretations of pathogenicity, Affects, association, risk factor
  Assembly: GRCh38
  Chromosome/Position: 16:89919709
  OMIM Allelic Variant: 155555.0004

- OCULOCUTANEOUS ALBINISM, TYPE II, MODIFIER OF

  ### OCULOCUTANEOUS ALBINISM, TYPE II, MODIFIER OF

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 5
  Clinical Significance: Conflicting interpretations of pathogenicity, Affects, association, risk factor
  Assembly: GRCh38
  Chromosome/Position: 16:89919709
  OMIM Allelic Variant: 155555.0004

- Skin/hair/eye pigmentation 2, red hair/fair skin

  ### Skin/hair/eye pigmentation 2, red hair/fair skin

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 5
  Clinical Significance: Conflicting interpretations of pathogenicity, Affects, association, risk factor
  Assembly: GRCh38
  Chromosome/Position: 16:89919709
  OMIM Allelic Variant: 155555.0004

- not provided

  ### not provided

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 5
  Clinical Significance: Conflicting interpretations of pathogenicity, Affects, association, risk factor
  Assembly: GRCh38
  Chromosome/Position: 16:89919709
  OMIM Allelic Variant: 155555.0004

- not specified

  ### not specified

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 5
  Clinical Significance: Conflicting interpretations of pathogenicity, Affects, association, risk factor
  Assembly: GRCh38
  Chromosome/Position: 16:89919709
  OMIM Allelic Variant: 155555.0004

Insufficiently evaluated benign — The MC1R gene encodes for a receptor protein for a melanin-stimulating hormone, so it is involved in melanogenesis (melanin production). Polymorphisms of this gene have been shown to cause increased susceptibility of skin cells to UV damage. Arg151Cys has been associated with melanoma.

Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (49)

Hetero

CT

Gene: CLEC7A
Variant: c.714T>G
(p.Tyr238Ter)
rsID: rs16910526
Ref Allele: A
Alt Allele: C
Freq: 5.5181%
CADD: 40

ClinVar Submissions (2)

- Aspergillosis, susceptibility to

  ### Aspergillosis, susceptibility to

  Aspergillus species are ubiquitous in nature and cause a wide spectrum of diseases, including saprophytic colonization of existing cavities (aspergilloma), allergic asthma, hypersensitivity pneumonitis, allergic bronchopulmonary aspergillosis, and disseminated disease associated with high mortality rates in patients with hematologic malignancies and recipients of solid organs and stem cell transplantations. Immunocompetent and nonatopic individuals are relatively resistant to infection, and disease occurs in the setting of host damage. Association of persistent inflammation with intractable infection is common in nonneutropenic patients after hematopoietic stem cell transplantation, as well as in allergic fungal diseases. The pathophysiology underlying Aspergillus infection highlights the bipolar nature of the inflammatory process in infection, in which early inflammation prevents or limits infection, but an uncontrolled response may oppose disease eradication (summary by Cunha et al., 2010). For information on familial occurrence of allergic bronchopulmonary aspergillosis, see 103920.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 29, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 12:10118488
  OMIM Allelic Variant: 606264.0001

- Familial chronic mucocutaneous candidiasis, Autosomal recessive

  ### Familial chronic mucocutaneous candidiasis

  Familial candidiasis is an inherited tendency to develop infections caused by a type of fungus called Candida. Affected individuals typically have infections of the skin, the nails, and the moist lining of body cavities (mucous membranes). These infections are recurrent and persistent, which means they come back repeatedly and can last a long time. This pattern of infection is called chronic mucocutaneous candidiasis.Candida is commonly present on the skin and on the mucous membranes, and in most people usually causes no health problems. However, certain medications (such as antibiotics and corticosteroids) and other factors can lead to occasional overgrowth of Candida (candidiasis) in the mouth (where it is known as thrush) or in the vagina. These episodes, commonly called yeast infections, usually last only a short time before being cleared by a healthy immune system.Most people with familial candidiasis have chronic or recurrent yeast infections that begin in early childhood. Skin infections lead to a rash with crusty, thickened patches; when these patches occur on the scalp, they can cause loss of hair in the affected area (scarring alopecia). Candidiasis of the nails can result in thick, cracked, and discolored nails and swelling and redness of the surrounding skin. Thrush and gastrointestinal symptoms such as bloating, constipation, or diarrhea are common in affected individuals. Women with familial candidiasis can develop frequent vaginal yeast infections, and infants can have yeast infections on the skin that cause persistent diaper rash.Depending on the genetic change involved in this condition, some affected individuals are at risk for developing systemic candidiasis, a more severe condition in which the infection spreads through the bloodstream to various organs including the brain and the meninges, which are the membranes covering the brain and spinal cord. Systemic candidiasis can be life-threatening.Chronic or recurrent yeast infections can occur in people without familial candidiasis. Some individuals experience recurrent candidiasis as part of a general susceptibility to infections because their immune systems are impaired by a disease such as acquired immune deficiency syndrome (AIDS) or severe combined immunodeficiency (SCID), medications, or other factors. Other individuals have syndromes such as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) or autosomal dominant hyper-IgE syndrome (AD-HIES) that include a tendency to develop candidiasis along with other signs and symptoms affecting various organs and systems of the body.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 29, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 12:10118488
  OMIM Allelic Variant: 606264.0001

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 29, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 12:10118488
  OMIM Allelic Variant: 606264.0001

Low clinical importance, Uncertain pathogenic — This variant has been found to impair homan mucosal antifungal defense and was implicated in vulvovaginal candidiasis and mucocutaneous infections in a Dutch family.

Clinically Significant Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (11)

Hetero

AC

Gene: ABCG5;ABCG8
Variant: c.55G>C
(p.Asp19His)
rsID: rs11887534
Ref Allele: G
Alt Allele: C
Freq: 6.3663%
CADD: 23

ClinVar Submissions (3)

- Gallbladder disease 4, Polygenic

  ### Gallbladder disease 4

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 2:43839108
  OMIM Allelic Variant: 605460.0009

- Sitosterolemia, Autosomal recessive

  ### Sitosterolemia

  Sitosterolemia is characterized by: Tendon xanthomas or tuberous (i.e., planar) xanthomas that can occur in childhood and in unusual locations (heels, knees, elbows and buttocks); Premature atherosclerosis which can lead to angina, aortic valve involvement, myocardial infarction, and sudden death; Hemolytic anemia, abnormally shaped erythrocytes (stomatocytes), and large platelets (macrothrombocytopenia). On occasion, the abnormal hematologic findings may be the initial presentation. The phenotypic spectrum of sitosterolemia is probably not fully appreciated due to underdiagnosis and the fact that clinical findings in infants are likely to be highly dependent on diet.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 2:43839108
  OMIM Allelic Variant: 605460.0009

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 2:43839108
  OMIM Allelic Variant: 605460.0009

Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (26)

Hetero

GC

Gene: GALT
Variant: c.940A>G
(p.Asn314Asp)
rsID: rs2070074
Ref Allele: A
Alt Allele: G
Freq: 6.6665%
CADD: 20.3

ClinVar Submissions (13)

- Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase

  ### Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 13, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 13
  Clinical Significance: Conflicting interpretations of pathogenicity, other
  Assembly: GRCh38
  Chromosome/Position: 9:34649445
  OMIM Allelic Variant: 606999.0005

- Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase

  ### Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 13, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 13
  Clinical Significance: Conflicting interpretations of pathogenicity, other
  Assembly: GRCh38
  Chromosome/Position: 9:34649445
  OMIM Allelic Variant: 606999.0005

- GALT POLYMORPHISM (DUARTE, D2)

  ### GALT POLYMORPHISM (DUARTE, D2)

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 13, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 13
  Clinical Significance: Conflicting interpretations of pathogenicity, other
  Assembly: GRCh38
  Chromosome/Position: 9:34649445
  OMIM Allelic Variant: 606999.0005

- GALT POLYMORPHISM (LOS ANGELES, D1)

  ### GALT POLYMORPHISM (LOS ANGELES, D1)

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 13, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 13
  Clinical Significance: Conflicting interpretations of pathogenicity, other
  Assembly: GRCh38
  Chromosome/Position: 9:34649445
  OMIM Allelic Variant: 606999.0005

- Galactosemia

  ### Galactosemia

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 13, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 13
  Clinical Significance: Conflicting interpretations of pathogenicity, other
  Assembly: GRCh38
  Chromosome/Position: 9:34649445
  OMIM Allelic Variant: 606999.0005

- not provided

  ### not provided

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 13, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 13
  Clinical Significance: Conflicting interpretations of pathogenicity, other
  Assembly: GRCh38
  Chromosome/Position: 9:34649445
  OMIM Allelic Variant: 606999.0005

- not specified

  ### not specified

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 13, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 13
  Clinical Significance: Conflicting interpretations of pathogenicity, other
  Assembly: GRCh38
  Chromosome/Position: 9:34649445
  OMIM Allelic Variant: 606999.0005

Low clinical importance, Uncertain benign — This variant has an allele frequency of ~8% and is ancestral to "Duarte" / "Duarte 2" and "Duarte 1"/"Los Angeles" galactosemia variants. This variant is evolutionarily ancestral, and in vitro studies fail to support an impact of this variant on enzyme activity. Carney et al. instead implicate a 4 base deletion on the 5' of the GALT gene as being causal and linked to this variant. Galactosemia is typically screened and detected in infants and causes early, severe but nonspecific symptoms (digestive problems, lethargy, failure to thrive).

Expert Reviewed Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (28)

Hetero

AG

Gene: FECH
Variant: c.315-48T>C
rsID: rs2272783
Ref Allele: A
Alt Allele: G
Freq: 7.2288%
CADD: 5.052

ClinVar Submissions (4)

- Erythema

  ### Erythema

  Red discoloration of the skin caused by infectious agents, inflammation, drug hypersensitivity, or underlying disease.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 22, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 4
  Clinical Significance: Pathogenic
  Assembly: GRCh38
  Chromosome/Position: 18:57571588
  OMIM Allelic Variant: 612386.0015

- Erythropoietic protoporphyria, Autosomal recessive

  ### Erythropoietic protoporphyria

  Erythropoietic protoporphyria (EPP) is characterized by cutaneous photosensitivity (usually beginning in infancy or childhood) that results in tingling, burning, pain, and itching within 30 minutes after exposure to sun or ultraviolet light and may be accompanied by swelling and redness. Symptoms (which may seem out of proportion to the visible skin lesions) may persist for hours or days after the initial phototoxic reaction. Photosensitivity remains for life. Multiple episodes of acute photosensitivity may lead to chronic changes of sun-exposed skin (lichenification, leathery pseudovesicles, grooving around the lips) and loss of lunulae of the nails. Approximately 20%-30% of individuals with EPP have some degree of liver dysfunction, which is typically mild with slight elevations of the liver enzymes. Up to 5% may develop more advanced liver disease which may be accompanied by motor neuropathy similar to that seen in the acute porphyrias.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 22, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 4
  Clinical Significance: Pathogenic
  Assembly: GRCh38
  Chromosome/Position: 18:57571588
  OMIM Allelic Variant: 612386.0015

- Jaundice

  ### Jaundice

  A clinical manifestation of HYPERBILIRUBINEMIA, characterized by the yellowish staining of the SKIN; MUCOUS MEMBRANE; and SCLERA. Clinical jaundice usually is a sign of LIVER dysfunction.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 22, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 4
  Clinical Significance: Pathogenic
  Assembly: GRCh38
  Chromosome/Position: 18:57571588
  OMIM Allelic Variant: 612386.0015

Clinically Significant Pathogenic

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (8)

Hetero

AG

Gene: AMPD1
Variant: c.133C>T
(p.Gln45Ter)
rsID: rs17602729
Ref Allele: G
Alt Allele: A
Freq: 8.0697%
CADD: 36

ClinVar Submissions (6)

- Muscle AMP deaminase deficiency, Autosomal recessive

  ### Muscle AMP deaminase deficiency

  Myoadenylate deaminase deficiency (MMDD) is an autosomal recessive condition that can manifest as exercise-induced muscle pain, occasionally associated with rhabdomyolysis and/or increased serum creatine kinase, or even infantile hypotonia. However, the finding of homozygous mutations among asymptomatic individuals have suggested to some (e.g., Verzijl et al., 1998) that AMPD1 deficiency may be a harmless entity (summary by Castro-Gago et al., 2011). Genetta et al. (2001) stated that AMPD1 deficiency is the most prevalent genetic disease in humans, the number of people heterozygous approaching 10% of Caucasians and individuals of African descent (Sabina et al., 1989). A small percentage of homozygous-deficient individuals, approximately 1.8% of the population, display symptoms of chronic fatigue and lost productivity as well as a predisposition to stress-related ailments, including heart disease and stroke, according to Genetta et al. (2001).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 27, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 6
  Clinical Significance: Conflicting interpretations of pathogenicity, other
  Assembly: GRCh38
  Chromosome/Position: 1:114693436
  OMIM Allelic Variant: 102770.0001

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 27, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 6
  Clinical Significance: Conflicting interpretations of pathogenicity, other
  Assembly: GRCh38
  Chromosome/Position: 1:114693436
  OMIM Allelic Variant: 102770.0001

Low clinical importance, Likely pathogenic — Causes Adenosine Deaminase Deficiency in a recessive manner. Most of the time individuals do not report symptoms, but when symptoms do exist they to be post-exercise symptoms of muscle weakness, muscle pain, and getting tired more quickly.

Expert Reviewed Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (17)

Homo

AA

Gene: GATA4
Variant: c.1129A>G
(p.Ser377Gly)
rsID: rs3729856
Ref Allele: A
Alt Allele: G
Freq: 8.186%
CADD: 4.477

ClinVar Submissions (3)

- Cardiovascular phenotype

  ### Cardiovascular phenotype

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 13, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 8:11757066

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 13, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 8:11757066

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 13, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 8:11757066

Clinically Significant Benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OpenSNP
- PubMed (2)

Hetero

AG

Gene: LDLR
Variant: c.1171G>A
(p.Ala391Thr)
rsID: rs11669576
Ref Allele: G
Alt Allele: A
Freq: 8.315%
CADD: 7.75

ClinVar Submissions (15)

- Familial hypercholesterolemia, Autosomal dominant

  ### Familial hypercholesterolemia

  Familial hypercholesterolemia (FH) is characterized by severely elevated LDL cholesterol (LDL-C) levels that lead to atherosclerotic plaque deposition in the coronary arteries and proximal aorta at an early age, leading to an increased risk for cardiovascular disease. Xanthomas (patches of yellowish cholesterol buildup) may worsen with age as a result of extremely high cholesterol levels. Xanthomas can occur around the eyelids and within the tendons of the elbows, hands, knees, and feet. In FH, the more common cardiovascular disease is coronary artery disease (CAD), which may manifest as angina and myocardial infarction; stroke occurs more rarely. Untreated men are at a 50% risk for a fatal or non-fatal coronary event by age 50 years; untreated women are at a 30% risk by age 60 years. An estimated 70%-95% of FH results from a heterozygous pathogenic variant in one of three genes (APOB, LDLR, PCSK9). FH is the most common inherited cardiovascular disease, with a prevalence of 1:200-250. FH likely accounts for 2%-3% of myocardial infarctions in individuals younger than age 60 years. In contrast, homozygous FH (HoFH) results from biallelic (homozygous or compound heterozygous) pathogenic variants in one of these known genes (APOB, LDLR, PCSK9). Most individuals with HoFH experience severe CAD by their mid-20s and the rate of either death or coronary bypass surgery by the teenage years is high. Severe aortic stenosis is also common.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 18, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 15
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 19:11111624

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 18, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 15
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 19:11111624

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 18, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 15
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 19:11111624

Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (16)

Hetero

GA

Gene: GATA4
Variant: c.617-64G>C
rsID: rs10503425
Ref Allele: G
Alt Allele: C
Freq: 9.8592%
CADD: 0.73

ClinVar Submissions (1)

- Congenital heart disease

  ### Congenital heart disease

  Critical congenital heart disease (CCHD) is a term that refers to a group of serious heart defects that are present from birth. These abnormalities result from problems with the formation of one or more parts of the heart during the early stages of embryonic development. CCHD prevents the heart from pumping blood effectively or reduces the amount of oxygen in the blood. As a result, organs and tissues throughout the body do not receive enough oxygen, which can lead to organ damage and life-threatening complications. Individuals with CCHD usually require surgery soon after birth.Although babies with CCHD may appear healthy for the first few hours or days of life, signs and symptoms soon become apparent. These can include an abnormal heart sound during a heartbeat (heart murmur), rapid breathing (tachypnea), low blood pressure (hypotension), low levels of oxygen in the blood (hypoxemia), and a blue or purple tint to the skin caused by a shortage of oxygen (cyanosis). If untreated, CCHD can lead to shock, coma, and death. However, most people with CCHD now survive past infancy due to improvements in early detection, diagnosis, and treatment.Some people with treated CCHD have few related health problems later in life. However, long-term effects of CCHD can include delayed development and reduced stamina during exercise. Adults with these heart defects have an increased risk of abnormal heart rhythms, heart failure, sudden cardiac arrest, stroke, and premature death.Each of the heart defects associated with CCHD affects the flow of blood into, out of, or through the heart. Some of the heart defects involve structures within the heart itself, such as the two lower chambers of the heart (the ventricles) or the valves that control blood flow through the heart. Others affect the structure of the large blood vessels leading into and out of the heart (including the aorta and pulmonary artery). Still others involve a combination of these structural abnormalities.People with CCHD have one or more specific heart defects. The heart defects classified as CCHD include coarctation of the aorta, double-outlet right ventricle, D-transposition of the great arteries, Ebstein anomaly, hypoplastic left heart syndrome, interrupted aortic arch, pulmonary atresia with intact septum, single ventricle, total anomalous pulmonary venous connection, tetralogy of Fallot, tricuspid atresia, and truncus arteriosus.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 07, 2017
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Pathogenic
  Assembly: GRCh38
  Chromosome/Position: 8:11748855

Clinically Significant Pathogenic

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (2)

Hetero

GC

Gene: EHBP1
Variant: c.1185+30064G>A
rsID: rs721048
Ref Allele: G
Alt Allele: A
Freq: 12.8002%
CADD: 2.618

ClinVar Submissions (1)

- Prostate cancer, hereditary, 12

  ### Prostate cancer, hereditary, 12

  Prostate cancer is a common disease that affects men, usually in middle age or later. In this disorder, certain cells in the prostate become abnormal and multiply without control or order to form a tumor. The prostate is a gland that surrounds the male urethra and helps produce semen, the fluid that carries sperm.Early prostate cancer usually does not cause pain, and most affected men exhibit no noticeable symptoms. Men are often diagnosed as the result of health screenings, such as a blood test for a substance called prostate specific antigen (PSA) or a medical procedure called a digital rectal exam. As the tumor grows larger, signs and symptoms can include difficulty starting or stopping the flow of urine, a feeling of not being able to empty the bladder completely, blood in the urine or semen, or pain with ejaculation. However, these changes can also occur with many other genitourinary conditions. Having one or more of these symptoms does not necessarily mean that a man has prostate cancer.The severity and outcome of prostate cancer varies widely. Early-stage prostate cancer can usually be treated successfully, and some older men have prostate tumors that grow so slowly that they may never cause health problems during their lifetime, even without treatment. In other men, however, the cancer is much more aggressive; in these cases, prostate cancer can be life-threatening.Some cancerous tumors can invade surrounding tissue and spread to other parts of the body. Tumors that begin at one site and then spread to other areas of the body are called metastatic cancers. The signs and symptoms of metastatic cancer depend on where the disease has spread. If prostate cancer spreads, cancerous cells most often appear in the lymph nodes, bones, lungs, liver, or brain. Bone metastases of prostate cancer most often cause pain in the lower back, pelvis, or hips.A small percentage of all prostate cancers cluster in families. These hereditary cancers are associated with inherited gene mutations. Hereditary prostate cancers tend to develop earlier in life than non-inherited (sporadic) cases.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 01, 2008
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Pathogenic
  Assembly: GRCh38
  Chromosome/Position: 2:62904596
  OMIM Allelic Variant: 609922.0001

Clinically Significant Pathogenic

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (57)

Hetero

GA

Gene: GNPAT
Variant: c.1556A>G
(p.Asp519Gly)
rsID: rs11558492
Ref Allele: A
Alt Allele: G
Freq: 16.5934%
CADD: 22.1

ClinVar Submissions (6)

- Rhizomelic chondrodysplasia punctata

  ### Rhizomelic chondrodysplasia punctata

  An autosomal recessive form of CHONDRODYSPLASIA PUNCTATA characterized by defective plasmalogen biosynthesis and impaired peroxisomes. Patients have shortened proximal limbs and severely disturbed endochondral bone formation. The metabolic defects associated with the impaired peroxisomes are present only in the rhizomelic form of chondrodysplasia punctata. (From Scriver et al, Metabolic Basis of Inherited Disease, 6th ed, p1497)

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 27, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 6
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 1:231272345
  OMIM Allelic Variant: 602744.0006

- Rhizomelic chondrodysplasia punctata type 2, Autosomal recessive

  ### Rhizomelic chondrodysplasia punctata type 2

  Rhizomelic chondrodysplasia punctata (RCDP) is a peroxisomal disorder characterized by disproportionately short stature primarily affecting the proximal parts of the extremities, a typical facial appearance including a broad nasal bridge, epicanthus, high-arched palate, dysplastic external ears, and micrognathia, congenital contractures, characteristic ocular involvement, dwarfism, and severe mental retardation with spasticity. Biochemically, plasmalogen synthesis and phytanic acid alpha-oxidation are defective. Most patients die in the first decade of life. RCDP1 (215100) is the most frequent form of RCDP (summary by Wanders and Waterham, 2005). Whereas RCDP1 is a peroxisomal biogenesis disorder (PBD), RCDP2 is classified as a single peroxisome enzyme deficiency (Waterham and Ebberink, 2012). For a discussion of genetic heterogeneity of rhizomelic chondrodysplasia punctata, see 215100.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 27, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 6
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 1:231272345
  OMIM Allelic Variant: 602744.0006

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 27, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 6
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 1:231272345
  OMIM Allelic Variant: 602744.0006

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 27, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 6
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 1:231272345
  OMIM Allelic Variant: 602744.0006

Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (9)

Hetero

AG

Gene: ACADS
Variant: c.625G>A
(p.Gly209Ser)
rsID: rs1799958
Ref Allele: G
Alt Allele: A
Freq: 19.974%
CADD: 28.1

ClinVar Submissions (8)

- Deficiency of butyryl-CoA dehydrogenase, Autosomal recessive

  ### Deficiency of butyryl-CoA dehydrogenase

  Most infants with short-chain acyl-CoA dehydrogenase deficiency (SCADD) identified through newborn screening programs have remained well, and asymptomatic relatives who meet diagnostic criteria are reported. Thus, SCADD is now viewed as a biochemical phenotype rather than a disease. A broad range of clinical findings was originally reported in those with confirmed SCADD, including severe dysmorphic facial features, feeding difficulties / failure to thrive, metabolic acidosis, ketotic hypoglycemia, lethargy, developmental delay, seizures, hypotonia, dystonia, and myopathy. However, individuals with no symptoms were also reported. In a large series of affected individuals detected on metabolic evaluation for developmental delay, 20% had failure to thrive, feeding difficulties, and hypotonia; 22% had seizures; and 30% had hypotonia without seizures. In contrast, the majority of infants with SCADD have been detected by expanded newborn screening, and the great majority of these infants remain asymptomatic. As with other fatty acid oxidation deficiencies, characteristic biochemical findings of SCADD may be absent except during times of physiologic stress such as fasting and illness. A diagnosis of SCADD based on clinical findings should not preclude additional testing to look for other causes.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 04, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 8
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 12:120738280
  OMIM Allelic Variant: 606885.0007

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 04, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 8
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 12:120738280
  OMIM Allelic Variant: 606885.0007

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 04, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 8
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 12:120738280
  OMIM Allelic Variant: 606885.0007

Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (8)

Homo

AA

Gene: FECH
Variant: c.68-23C>T
rsID: rs2269219
Ref Allele: G
Alt Allele: A
Freq: 27.9697%
CADD: 1.754

ClinVar Submissions (2)

- Erythema

  ### Erythema

  Red discoloration of the skin caused by infectious agents, inflammation, drug hypersensitivity, or underlying disease.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 25, 2016
  Review Status: no assertion criteria provided
  Number of Submitters: 2
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 18:57580222
  OMIM Allelic Variant: 612386.0003

- Erythropoietic protoporphyria, Autosomal recessive

  ### Erythropoietic protoporphyria

  Erythropoietic protoporphyria (EPP) is characterized by cutaneous photosensitivity (usually beginning in infancy or childhood) that results in tingling, burning, pain, and itching within 30 minutes after exposure to sun or ultraviolet light and may be accompanied by swelling and redness. Symptoms (which may seem out of proportion to the visible skin lesions) may persist for hours or days after the initial phototoxic reaction. Photosensitivity remains for life. Multiple episodes of acute photosensitivity may lead to chronic changes of sun-exposed skin (lichenification, leathery pseudovesicles, grooving around the lips) and loss of lunulae of the nails. Approximately 20%-30% of individuals with EPP have some degree of liver dysfunction, which is typically mild with slight elevations of the liver enzymes. Up to 5% may develop more advanced liver disease which may be accompanied by motor neuropathy similar to that seen in the acute porphyrias.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 25, 2016
  Review Status: no assertion criteria provided
  Number of Submitters: 2
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 18:57580222
  OMIM Allelic Variant: 612386.0003

- Jaundice

  ### Jaundice

  A clinical manifestation of HYPERBILIRUBINEMIA, characterized by the yellowish staining of the SKIN; MUCOUS MEMBRANE; and SCLERA. Clinical jaundice usually is a sign of LIVER dysfunction.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 25, 2016
  Review Status: no assertion criteria provided
  Number of Submitters: 2
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 18:57580222
  OMIM Allelic Variant: 612386.0003

Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (3)

Hetero

GA

Gene: CCL2
Variant: g.2493A>G
rsID: rs1024611
Ref Allele: A
Alt Allele: G
Freq: 28.6514%
CADD: 3.208

ClinVar Submissions (1)

- Coronary artery disease, development of, in hiv

  ### Coronary artery disease, development of, in hiv

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 15, 2009
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Pathogenic, risk factor
  Assembly: GRCh38
  Chromosome/Position: 17:34252769
  OMIM Allelic Variant: 158105.0003

- Coronary artery disease, modifier of

  ### Coronary artery disease, modifier of

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 15, 2009
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Pathogenic, risk factor
  Assembly: GRCh38
  Chromosome/Position: 17:34252769
  OMIM Allelic Variant: 158105.0003

- Mycobacterium tuberculosis, susceptibility to

  ### Mycobacterium tuberculosis, susceptibility to

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 15, 2009
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Pathogenic, risk factor
  Assembly: GRCh38
  Chromosome/Position: 17:34252769
  OMIM Allelic Variant: 158105.0003

- Spina bifida, susceptibility to

  ### Spina bifida, susceptibility to

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 15, 2009
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Pathogenic, risk factor
  Assembly: GRCh38
  Chromosome/Position: 17:34252769
  OMIM Allelic Variant: 158105.0003

Clinically Significant Pathogenic, risk factor

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (91)

Hetero

AG

Gene: GCDH
Variant: c.852+223C>T
rsID: rs11085825
Ref Allele: C
Alt Allele: T
Freq: 30.6846%
CADD: 1.467

ClinVar Submissions (1)

- Glutaric aciduria, type 1, Autosomal recessive

  ### Glutaric aciduria, type 1

  Glutaric acidemia I is an autosomal recessive metabolic disorder characterized by gliosis and neuronal loss in the basal ganglia and a progressive movement disorder that usually begins during the first year of life (Goodman et al., 1995). Hedlund et al. (2006) provided a detailed review of the clinical and biochemical aspects of glutaric acidemia type I.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 08, 2015
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Likely pathogenic
  Assembly: GRCh38
  Chromosome/Position: 19:12896644

Clinically Significant Likely pathogenic

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: GCDH
Variant: c.*288G>T
rsID: rs9384
Ref Allele: G
Alt Allele: T
Freq: 33.4719%
CADD: 1.464

ClinVar Submissions (2)

- Glutaric acidemia

  ### Glutaric acidemia

  An increased concentration of glutaric acid in the blood.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 19:12899829

- Glutaric aciduria, type 1, Autosomal recessive

  ### Glutaric aciduria, type 1

  Glutaric acidemia I is an autosomal recessive metabolic disorder characterized by gliosis and neuronal loss in the basal ganglia and a progressive movement disorder that usually begins during the first year of life (Goodman et al., 1995). Hedlund et al. (2006) provided a detailed review of the clinical and biochemical aspects of glutaric acidemia type I.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 19:12899829

Clinically Significant Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

GT

Gene: CCDC170
Variant: c.1810G>A
(p.Val604Ile)
rsID: rs6929137
Ref Allele: G
Alt Allele: A
Freq: 37.1743%
CADD: 4.328

ClinVar Submissions (1)

- Estrogen resistance, Autosomal recessive

  ### Estrogen resistance

  Estrogen resistance (ESTRR) is characterized by absence of puberty with elevated estradiol and gonadotropic hormones, as well as markedly delayed bone maturation. Female patients show absent breast development, small uterus, and enlarged multicystic ovaries; male patients may show small testes (Bernard et al., 2017). Some patients exhibit continued growth into adulthood (Smith et al., 1994).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 01, 2014
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Likely pathogenic
  Assembly: GRCh38
  Chromosome/Position: 6:151615542

Clinically Significant Likely pathogenic

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (18)

Hetero

GA

Gene: GATA4
Variant: c.1147-107A>G
rsID: rs745379
Ref Allele: A
Alt Allele: G
Freq: 38.0105%
CADD: 2.248

ClinVar Submissions (1)

- Congenital heart disease

  ### Congenital heart disease

  Critical congenital heart disease (CCHD) is a term that refers to a group of serious heart defects that are present from birth. These abnormalities result from problems with the formation of one or more parts of the heart during the early stages of embryonic development. CCHD prevents the heart from pumping blood effectively or reduces the amount of oxygen in the blood. As a result, organs and tissues throughout the body do not receive enough oxygen, which can lead to organ damage and life-threatening complications. Individuals with CCHD usually require surgery soon after birth.Although babies with CCHD may appear healthy for the first few hours or days of life, signs and symptoms soon become apparent. These can include an abnormal heart sound during a heartbeat (heart murmur), rapid breathing (tachypnea), low blood pressure (hypotension), low levels of oxygen in the blood (hypoxemia), and a blue or purple tint to the skin caused by a shortage of oxygen (cyanosis). If untreated, CCHD can lead to shock, coma, and death. However, most people with CCHD now survive past infancy due to improvements in early detection, diagnosis, and treatment.Some people with treated CCHD have few related health problems later in life. However, long-term effects of CCHD can include delayed development and reduced stamina during exercise. Adults with these heart defects have an increased risk of abnormal heart rhythms, heart failure, sudden cardiac arrest, stroke, and premature death.Each of the heart defects associated with CCHD affects the flow of blood into, out of, or through the heart. Some of the heart defects involve structures within the heart itself, such as the two lower chambers of the heart (the ventricles) or the valves that control blood flow through the heart. Others affect the structure of the large blood vessels leading into and out of the heart (including the aorta and pulmonary artery). Still others involve a combination of these structural abnormalities.People with CCHD have one or more specific heart defects. The heart defects classified as CCHD include coarctation of the aorta, double-outlet right ventricle, D-transposition of the great arteries, Ebstein anomaly, hypoplastic left heart syndrome, interrupted aortic arch, pulmonary atresia with intact septum, single ventricle, total anomalous pulmonary venous connection, tetralogy of Fallot, tricuspid atresia, and truncus arteriosus.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 07, 2017
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Pathogenic
  Assembly: GRCh38
  Chromosome/Position: 8:11758186

Clinically Significant Pathogenic

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

AG

Gene: -
Variant: g.198807802C>A
rsID: rs9660525
Ref Allele: C
Alt Allele: A
Freq: 38.3649%
CADD: 1.095

ClinVar Submissions (1)

- Acute myeloid leukemia with maturation

  ### Acute myeloid leukemia with maturation

  An acute myeloid leukemia (AML) characterized by blasts with evidence of maturation to more mature neutrophils. (WHO, 2001)

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Pathogenic
  Assembly: GRCh38
  Chromosome/Position: 1:198807802

Clinically Significant Pathogenic

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CA

Gene: UROS
Variant: c.-219C>A
rsID: rs4385801
Ref Allele: G
Alt Allele: T
Freq: 40.7015%
CADD: 5.844

ClinVar Submissions (2)

- Congenital erythropoietic porphyria, Autosomal recessive

  ### Congenital erythropoietic porphyria

  Congenital erythropoietic porphyria (CEP) is characterized in most individuals by severe cutaneous photosensitivity with blistering and increased friability of the skin over light-exposed areas. Onset in most affected individuals occurs at birth or early infancy. The first manifestation is often pink to dark red discoloration of the urine. Hemolytic anemia is common and can range from mild to severe, with some affected individuals requiring chronic blood transfusions. Porphyrin deposition may lead to corneal ulcers and scarring, reddish-brown discoloration of the teeth (erythrodontia), and mild bone loss and/or expansion of the bone marrow. The phenotypic spectrum, however, is broad and ranges from non-immune hydrops fetalis in utero to late-onset disease with only mild cutaneous manifestations in adulthood.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 10:125823221

Clinically Significant Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (3)

Homo

TT

Gene: CCDC170
Variant: g.151627231G>A
rsID: rs2046210
Ref Allele: G
Alt Allele: A
Freq: 42.4017%
CADD: 0.277

ClinVar Submissions (1)

- Estrogen resistance, Autosomal recessive

  ### Estrogen resistance

  Estrogen resistance (ESTRR) is characterized by absence of puberty with elevated estradiol and gonadotropic hormones, as well as markedly delayed bone maturation. Female patients show absent breast development, small uterus, and enlarged multicystic ovaries; male patients may show small testes (Bernard et al., 2017). Some patients exhibit continued growth into adulthood (Smith et al., 1994).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 01, 2014
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Likely pathogenic
  Assembly: GRCh38
  Chromosome/Position: 6:151627231

Expert Reviewed Clinically Significant Likely pathogenic

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (88)

Hetero

GA

Gene: CYP4V2
Variant: c.64C>G
(p.Leu22Val)
rsID: rs1055138
Ref Allele: C
Alt Allele: G
Freq: 45.4383%
CADD: 3.733

ClinVar Submissions (6)

- Bietti crystalline corneoretinal dystrophy, Autosomal recessive

  ### Bietti crystalline corneoretinal dystrophy

  Bietti crystalline dystrophy (BCD) is a chorioretinal degeneration characterized by the presence of yellow-white crystals and/or complex lipid deposits in the retina and (to a variable degree) the cornea. Progressive atrophy and degeneration of the retinal pigment epithelium (RPE) / choroid lead to symptoms similar to those of other forms of retinal degeneration that fall under the category of retinitis pigmentosa and allied disorders, namely: reduced visual acuity, poor night vision, abnormal retinal electrophysiology, visual field loss, and often impaired color vision. Marked asymmetry between eyes is not uncommon. Onset is typically during the second to third decade of life, but ranges from the early teenage years to beyond the third decade. With time, loss of peripheral visual field, central acuity, or both result in legal blindness in most if not all affected individuals.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 4:186191887

- Corneal Dystrophy, Recessive

  ### Corneal Dystrophy, Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 4:186191887

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 4:186191887

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 4:186191887

Clinically Significant Benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (3)

Homo

GG

Gene: COL4A4
Variant: c.3979G>A
(p.Val1327Met)
rsID: rs2229813
Ref Allele: C
Alt Allele: T
Freq: 46.2371%
CADD: 2.045

ClinVar Submissions (6)

- Alport syndrome

  ### Alport syndrome

  Alport syndrome is a genetic condition characterized by kidney disease, hearing loss, and eye abnormalities.People with Alport syndrome experience progressive loss of kidney function. Almost all affected individuals have blood in their urine (hematuria), which indicates abnormal functioning of the kidneys. Many people with Alport syndrome also develop high levels of protein in their urine (proteinuria). The kidneys become less able to function as this condition progresses, resulting in end-stage renal disease (ESRD).People with Alport syndrome frequently develop sensorineural hearing loss, which is caused by abnormalities of the inner ear, during late childhood or early adolescence. Affected individuals may also have misshapen lenses in the eyes (anterior lenticonus) and abnormal coloration of the light-sensitive tissue at the back of the eye (retina). These eye abnormalities seldom lead to vision loss.Significant hearing loss, eye abnormalities, and progressive kidney disease are more common in males with Alport syndrome than in affected females.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 09, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 2:227028004

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 09, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 2:227028004

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 09, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 2:227028004

Clinically Significant Benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OpenSNP
- PubMed (4)

Homo

TT

Gene: MIR181A1HG
Variant: n.364-18748G>A
rsID: rs12406470
Ref Allele: C
Alt Allele: T
Freq: 46.3358%
CADD: 2.063

ClinVar Submissions (1)

- Acute myeloid leukemia with maturation

  ### Acute myeloid leukemia with maturation

  An acute myeloid leukemia (AML) characterized by blasts with evidence of maturation to more mature neutrophils. (WHO, 2001)

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Pathogenic
  Assembly: GRCh38
  Chromosome/Position: 1:198826991

Clinically Significant Pathogenic

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CT

Gene: IL4R
Variant: c.223A>G
(p.Ile75Val)
rsID: rs1805010
Ref Allele: A
Alt Allele: G
Freq: 46.8758%
CADD: 7.656

ClinVar Submissions (1)

- Acquired immunodeficiency syndrome, slow progression to

  ### Acquired immunodeficiency syndrome, slow progression to

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 14, 2015
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Pathogenic, protective
  Assembly: GRCh38
  Chromosome/Position: 16:27344882
  OMIM Allelic Variant: 147781.0002

- Atopy, resistance to

  ### Atopy, resistance to

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 14, 2015
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Pathogenic, protective
  Assembly: GRCh38
  Chromosome/Position: 16:27344882
  OMIM Allelic Variant: 147781.0002

Clinically Significant Pathogenic, protective

- LitVar
- SNPedia
- dbSNP
- UniProt
- OpenSNP
- PubMed (54)

Homo

GG

Gene: CCR5
Variant: c.-301+246A>G
rsID: rs1799987
Ref Allele: A
Alt Allele: G
Freq: 49.3884%
CADD: 2.992

ClinVar Submissions (1)

- Acquired immunodeficiency syndrome, delayed progression to

  ### Acquired immunodeficiency syndrome, delayed progression to

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 08, 2003
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Conflicting interpretations of pathogenicity, protective
  Assembly: GRCh38
  Chromosome/Position: 3:46370444
  OMIM Allelic Variant: 601373.0006

- CCR5 PROMOTER POLYMORPHISM

  ### CCR5 PROMOTER POLYMORPHISM

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 08, 2003
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Conflicting interpretations of pathogenicity, protective
  Assembly: GRCh38
  Chromosome/Position: 3:46370444
  OMIM Allelic Variant: 601373.0006

- Human immunodeficiency virus type 1, susceptibility to

  ### Human immunodeficiency virus type 1, susceptibility to

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 08, 2003
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Conflicting interpretations of pathogenicity, protective
  Assembly: GRCh38
  Chromosome/Position: 3:46370444
  OMIM Allelic Variant: 601373.0006

Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (42)

Homo

GG

## Rare mutations

Below are rare variants (frequency less than 1%) that were submitted to ClinVar. The data presented has no guarantees of reporting accuracy. Heterozygous variants are reported as yellow and homozygous variants as red. A red or yellow variant does not necessarily mean one has or carries a condition or disease. This is for research and educational purposes only.

Gene: TTN
Variant: c.2076+13G>A
rsID: rs778505099
Ref Allele: C
Alt Allele: T
Freq: 0.0008%rare
CADD: 5.172

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 16, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:178789347

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CT

Gene: ATR
Variant: c.3946-104A>G
rsID: rs869312483
Ref Allele: T
Alt Allele: C
Freq: 0.0016%rare
CADD: 4.046

ClinVar Submissions (1)

- Hereditary cancer-predisposing syndrome

  ### Hereditary cancer-predisposing syndrome

  The condition of a pattern of malignancies within a family, but not every individual's necessarily having the same neoplasm. Characteristically the tumor tends to occur at an earlier than average age, individuals may have more than one primary tumor, the tumors may be multicentric, usually more than 25 percent of the individuals in direct lineal descent from the proband are affected, and the cancer predisposition in these families behaves as an autosomal dominant trait with about 60 percent penetrance.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 01, 2015
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 3:142524303

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

TC

Gene: BRAT1
Variant: c.1012C>G
(p.Pro338Ala)
rsID: rs373020561
Ref Allele: G
Alt Allele: C
Freq: 0.0016%rare
CADD: 0.752

ClinVar Submissions (1)

- Rigidity and multifocal seizure syndrome, lethal neonatal, Autosomal recessive

  ### Rigidity and multifocal seizure syndrome, lethal neonatal

  Lethal neonatal rigidity and multifocal seizure syndrome is a severe autosomal recessive epileptic encephalopathy characterized by onset of rigidity and intractable seizures at or soon after birth. Affected infants achieve no developmental milestones and die within the first months or years of life (summary by Saitsu et al., 2014).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 24, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 7:2542123

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GC

Gene: FBP1
Variant: c.915C>T
(p.Asp305=)
rsID: rs762285012
Ref Allele: G
Alt Allele: A
Freq: 0.0024%rare
CADD: 11.61

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 26, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 9:94603483

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: MARVELD2
Variant: c.1059A>G
(p.Ile353Met)
rsID: rs727503158
Ref Allele: A
Alt Allele: G
Freq: 0.0032%rare
CADD: 3.998

ClinVar Submissions (2)

- Nonsyndromic Hearing Loss, Recessive

  ### Nonsyndromic Hearing Loss, Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 2
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 5:69420444

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 2
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 5:69420444

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

AG

Gene: SOX9
Variant: c.-284G>A
rsID: rs773395160
Ref Allele: G
Alt Allele: A
Freq: 0.004%rare
CADD: 12.71

ClinVar Submissions (1)

- Camptomelic dysplasia, Autosomal dominant

  ### Camptomelic dysplasia

  Campomelic dysplasia (CD) is a skeletal dysplasia characterized by distinctive facies, Pierre Robin sequence with cleft palate, shortening and bowing of long bones, and clubfeet. Other findings include laryngotracheomalacia with respiratory compromise and ambiguous genitalia or normal female external genitalia in most individuals with a 46,XY karyotype. Many affected infants die in the neonatal period; additional problems identified in long-term survivors include short stature, cervical spine instability with cord compression, progressive scoliosis, and hearing impairment.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 17:72121108

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GA

Gene: ALMS1
Variant: c.7895C>T
(p.Ala2632Val)
rsID: rs1027248513
Ref Allele: C
Alt Allele: T
Freq: 0.0056%rare
CADD: 15.21

ClinVar Submissions (1)

- Alstrom syndrome, Autosomal recessive

  ### Alstrom syndrome

  Alström syndrome is characterized by cone-rod dystrophy, obesity, progressive sensorineural hearing impairment, dilated or restrictive cardiomyopathy, the insulin resistance syndrome, and multiple organ failure. Wide clinical variability is observed among affected individuals, even within the same family. Cone-rod dystrophy presents as progressive visual impairment, photophobia, and nystagmus usually starting between birth and age 15 months. Many individuals lose all perception of light by the end of the second decade, but a minority retain the ability to read large print into the third decade. Children usually have normal birth weight but develop truncal obesity during their first year. Progressive sensorineural hearing loss presents in the first decade in as many as 70% of individuals. Hearing loss may progress to the severe or moderately severe range (40-70 db) by the end of the first to second decade. Insulin resistance is typically accompanied by the skin changes of acanthosis nigricans, and proceeds to type 2 diabetes in the majority by the third decade. Nearly all demonstrate associated dyslipidemia. Other endocrine abnormalities can include hypothyroidism, hypogonadotropic hypogonadism in boys, and polycystic ovaries in girls. More than 60% of individuals with Alström syndrome develop cardiac failure as a result of dilated or restrictive cardiomyopathy. About 50% of individuals have delay in early developmental milestones; intelligence is normal. Liver involvement includes elevation of transaminases, steatosis, hepatosplenomegaly, and steatohepatitis. Portal hypertension and cirrhosis can lead to hepatic encephalopathy and life-threatening esophageal varices. Pulmonary dysfunction and severe renal disease may also develop. End-stage renal disease (ESRD) can occur as early as the late teens.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 01, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 2:73489851

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CT

Gene: COQ8A
Variant: c.1256+11C>G
rsID: rs564593360
Ref Allele: C
Alt Allele: G
Freq: 0.0064%rare
CADD: 0.021

ClinVar Submissions (1)

- Autosomal recessive cerebellar ataxia

  ### Autosomal recessive cerebellar ataxia

  Autosomal recessive cerebellar ataxias (ARCA) are a heterogeneous group of rare neurological disorders involving both the central and peripheral nervous system (and in some cases other systems and organs), and characterized by degeneration or abnormal development of the cerebellum and spinal cord and, in most cases, early onset occurring before the age of 20 years.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 1:226983865

- Coenzyme Q10 deficiency, Spinocerebellar Ataxia Type

  ### Coenzyme Q10 deficiency, Spinocerebellar Ataxia Type

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 1:226983865

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CG

Gene: SRD5A3
Variant: c.*2804C>T
rsID: rs886059484
Ref Allele: C
Alt Allele: T
Freq: 0.0072%rare
CADD: 2.051

ClinVar Submissions (1)

- Congenital disorder of glycosylation

  ### Congenital disorder of glycosylation

  A genetically heterogeneous group of heritable disorders resulting from defects in protein N-glycosylation.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 4:55372895

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CT

Gene: FANCA
Variant: c.2856G>C
(p.Gln952His)
rsID: rs200093209
Ref Allele: C
Alt Allele: G
Freq: 0.0072%rare
CADD: 6.55

ClinVar Submissions (1)

- Fanconi anemia

  ### Fanconi anemia

  Fanconi anemia (FA) is characterized by physical abnormalities, bone marrow failure, and increased risk for malignancy. Physical abnormalities, present in approximately 75% of affected individuals, include one or more of the following: short stature, abnormal skin pigmentation, skeletal malformations of the upper and lower limbs, microcephaly, and ophthalmic and genitourinary tract anomalies. Progressive bone marrow failure with pancytopenia typically presents in the first decade, often initially with thrombocytopenia or leukopenia. The incidence of acute myeloid leukemia is 13% by age 50 years. Solid tumors – particularly of the head and neck, skin, gastrointestinal tract, and genitourinary tract – are more common in individuals with FA.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 04, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 16:89758702

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CG

Gene: REEP1
Variant: c.*2261C>A
rsID: rs772358643
Ref Allele: G
Alt Allele: T
Freq: 0.0104%rare
CADD: 16.71

ClinVar Submissions (1)

- Spastic paraplegia, autosomal dominant

  ### Spastic paraplegia, autosomal dominant

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 2:86214839

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GT

Gene: KIF7
Variant: c.2337G>A
(p.Glu779=)
rsID: rs202089770
Ref Allele: C
Alt Allele: T
Freq: 0.0104%rare
CADD: 8.593

ClinVar Submissions (1)

- Acrocallosal syndrome, Schinzel type, Autosomal dominant

  ### Acrocallosal syndrome, Schinzel type

  Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 15:89642260

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CT

Gene: CHMP1A
Variant: c.*7C>T
rsID: rs768229451
Ref Allele: G
Alt Allele: A
Freq: 0.0111%rare
CADD: 3.274

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 12, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 16:89646059

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: SYNE2
Variant: c.15031A>G
(p.Ile5011Val)
rsID: rs201269146
Ref Allele: A
Alt Allele: G
Freq: 0.0119%rare
CADD: 18.98

ClinVar Submissions (1)

- Emery-Dreifuss muscular dystrophy 5, autosomal dominant, Autosomal dominant

  ### Emery-Dreifuss muscular dystrophy 5, autosomal dominant

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 02, 2018
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 14:64141395

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

AG

Gene: CLN6
Variant: c.585C>T
(p.Gly195=)
rsID: rs144507672
Ref Allele: G
Alt Allele: A
Freq: 0.0119%rare
CADD: 20.5

ClinVar Submissions (3)

- Neuronal Ceroid-Lipofuscinosis, Recessive

  ### Neuronal Ceroid-Lipofuscinosis, Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 21, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 15:68209717

- Neuronal ceroid lipofuscinosis, Autosomal dominant

  ### Neuronal ceroid lipofuscinosis

  The neuronal ceroid-lipofuscinoses (NCLs) are a group of inherited, neurodegenerative, lysosomal storage disorders characterized by progressive intellectual and motor deterioration, seizures, and early death. Visual loss is a feature of most forms. Clinical phenotypes have been characterized traditionally according to the age of onset and order of appearance of clinical features into infantile, late-infantile, juvenile, adult, and Northern epilepsy (also known as progressive epilepsy with mental retardation [EPMR]). There is however genetic and allelic heterogeneity; a proposed new nomenclature and classification system has been developed to take into account both the responsible gene and the age at disease onset; for example, CLN1 disease, infantile onset and CLN1 disease, juvenile onset are both caused by pathogenic variants in PPT1 but with differing age of onset. The most prevalent NCLs are CLN3 disease, classic juvenile and CLN2 disease, classic late infantile (although prevalence varies by ethnicity and country of family origin): CLN2 disease, classic late infantile. The first symptoms typically appear between age two and four years, usually starting with epilepsy, followed by regression of developmental milestones, myoclonic ataxia, and pyramidal signs. Visual impairment typically appears at age four to six years and rapidly progresses to light /dark awareness only. Life expectancy ranges from age six years to early teenage. CLN3 disease, classic juvenile. Onset is usually between ages four and ten years. Rapidly progressing visual loss resulting in severe visual impairment within one to two years is often the first clinical sign. Epilepsy with generalized tonic-clonic seizures and/or complex-partial seizures typically appears around age ten years. Life expectancy ranges from the late teens to the 30s. Other forms of NCL may present with behavior changes, epilepsy, visual impairment, or slowing of developmental progress and then loss of skills. The course may be extremely variable. Some genotype-phenotype information is available.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 21, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 15:68209717

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 21, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 15:68209717

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GA

Gene: GABRG2
Variant: c.107+12C>T
rsID: rs369466385
Ref Allele: C
Alt Allele: T
Freq: 0.0167%rare
CADD: 6.742

ClinVar Submissions (2)

- Generalized epilepsy with febrile seizures plus

  ### Generalized epilepsy with febrile seizures plus

  Genetic epilepsy with febrile seizures plus (GEFS+) is a spectrum of seizure disorders of varying severity. GEFS+ is usually diagnosed in families whose members have a combination of febrile seizures, which are triggered by a high fever, and recurrent seizures (epilepsy) of other types, including seizures that are not related to fevers (afebrile seizures). The additional seizure types usually involve both sides of the brain (generalized seizures); however, seizures that involve only one side of the brain (partial seizures) occur in some affected individuals. The most common types of seizure in people with GEFS+ include myoclonic seizures, which cause involuntary muscle twitches; atonic seizures, which involve sudden episodes of weak muscle tone; and absence seizures, which cause loss of consciousness for short periods that appear as staring spells.The most common and mildest feature of the GEFS+ spectrum is simple febrile seizures, which begin in infancy and usually stop by age 5. When the febrile seizures continue after age 5 or other types of seizure develop, the condition is called febrile seizures plus (FS+). Seizures in FS+ usually end in early adolescence.A condition called Dravet syndrome (also known as severe myoclonic epilepsy of infancy or SMEI) is often considered part of the GEFS+ spectrum and is the most severe disorder in this group. Affected infants typically have prolonged seizures lasting several minutes (status epilepticus), which are triggered by fever. Other seizure types, including afebrile seizures, begin in early childhood. These types can include myoclonic or absence seizures. In Dravet syndrome, these seizures are difficult to control with medication, and they can worsen over time. A decline in brain function is also common in Dravet syndrome. Affected individuals usually develop normally in the first year of life, but then development stalls, and some affected children lose already-acquired skills (developmental regression). Many people with Dravet syndrome have difficulty coordinating movements (ataxia) and intellectual disability.Some people with GEFS+ have seizure disorders of intermediate severity that may not fit into the classical diagnosis of simple febrile seizures, FS+, or Dravet syndrome.Family members with GEFS+ may have different combinations of febrile seizures and epilepsy. For example, one affected family member may have only febrile seizures, while another also has myoclonic epilepsy. While GEFS+ is usually diagnosed in families, it can occur in individuals with no history of the condition in their family.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 2
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 5:162068118

- Severe myoclonic epilepsy in infancy, Autosomal dominant

  ### Severe myoclonic epilepsy in infancy

  SCN1A-related seizure disorders encompass a spectrum that ranges from simple febrile seizures (FS) and generalized epilepsy with febrile seizures plus (GEFS+) at the mild end to Dravet syndrome and intractable childhood epilepsy with generalized tonic-clonic seizures (ICE-GTC) at the severe end. Phenotypes with intractable seizures including Dravet syndrome (also known as severe myoclonic epilepsy in infancy [SMEI] or polymorphic myoclonic epilepsy in infancy [PMEI]) are usually associated with progressive dementia. Less commonly observed phenotypes include myoclonic-astatic epilepsy (MAE or Doose syndrome), Lennox-Gastaut syndrome (LGS), infantile spasms, and vaccine-related encephalopathy and seizures. The phenotype of SCN1A-related seizure disorders can vary even within the same family.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 2
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 5:162068118

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 2
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 5:162068118

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CT

Gene: ADAMTS2
Variant: c.724G>A
(p.Ala242Thr)
rsID: rs372103269
Ref Allele: C
Alt Allele: T
Freq: 0.0191%rare
CADD: 1.265

ClinVar Submissions (3)

- Ehlers-Danlos syndrome, type vii, autosomal recessive, Autosomal recessive

  ### Ehlers-Danlos syndrome, type vii, autosomal recessive

  Dermatosparaxis (meaning 'tearing of skin') is an autosomal recessive disorder of connective tissue resulting from deficiency of procollagen peptidase, an enzyme that aids in the processing of type I procollagen. The disorder and the responsible biochemical defect was first observed in cattle (Lapiere et al., 1971). Lapiere and Nusgens (1993) reviewed the discovery of dermatosparaxis in cattle, the elucidation of the disorder, its occurrence in other animals, and the delayed recognition of the disorder in the human.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 18, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 5:179207680

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 18, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 5:179207680

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CT

Gene: NEB
Variant: c.6369G>A
(p.Thr2123=)
rsID: rs540542570
Ref Allele: C
Alt Allele: T
Freq: 0.0239%rare
CADD: 2.049

ClinVar Submissions (1)

- Nemaline Myopathy, Recessive

  ### Nemaline Myopathy, Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 2:151656279

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CT

Gene: LRBA
Variant: c.3499A>G
(p.Thr1167Ala)
rsID: rs146297781
Ref Allele: T
Alt Allele: C
Freq: 0.0295%rare
CADD: 8.126

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 10, 2015
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 4:150852211

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

TC

Gene: TERT
Variant: c.604G>A
(p.Ala202Thr)
rsID: rs121918661
Ref Allele: C
Alt Allele: T
Freq: 0.0303%rare
CADD: 1.552

ClinVar Submissions (8)

- Aplastic anemia

  ### Aplastic anemia

  Aplastic anemia is a serious disorder of the bone marrow that affects between 2 and 5 persons per million per year. About 75% of these cases are classified as idiopathic (Young, 2000). In about 15% of cases a drug or infection can be identified that precipitates the aplasia, although why only some individuals are susceptible is unclear. In about 5 to 10% of patients, the aplastic anemia is constitutional--i.e., is familial or presents with one or more associated somatic abnormalities (summary by Vulliamy et al., 2002).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 26, 2019
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 8
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 5:1294282
  OMIM Allelic Variant: 187270.0001

- Dyskeratosis congenita, autosomal dominant, 2, Autosomal dominant

  ### Dyskeratosis congenita, autosomal dominant, 2

  Dyskeratosis congenita (DC), a telomere biology disorder, is characterized by a classic triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia. The classic triad may not be present in all individuals. People with DC are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML), solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include: abnormal pigmentation changes not restricted to the upper chest and neck, eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), and dental abnormalities (caries, periodontal disease, taurodauntism). Although most persons with DC have normal psychomotor development and normal neurologic function, significant developmental delay is present in the two variants in which additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome). Onset and progression of manifestations of DC vary: at the mild end of the spectrum are those who have only minimal physical findings with normal bone marrow function, and at the severe end are those who have the diagnostic triad and early-onset BMF.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 26, 2019
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 8
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 5:1294282
  OMIM Allelic Variant: 187270.0001

- Dyskeratosis congenita, autosomal dominant, 2, Autosomal dominant

  ### Dyskeratosis congenita, autosomal dominant, 2

  Dyskeratosis congenita (DC), a telomere biology disorder, is characterized by a classic triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia. The classic triad may not be present in all individuals. People with DC are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML), solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include: abnormal pigmentation changes not restricted to the upper chest and neck, eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), and dental abnormalities (caries, periodontal disease, taurodauntism). Although most persons with DC have normal psychomotor development and normal neurologic function, significant developmental delay is present in the two variants in which additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome). Onset and progression of manifestations of DC vary: at the mild end of the spectrum are those who have only minimal physical findings with normal bone marrow function, and at the severe end are those who have the diagnostic triad and early-onset BMF.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 26, 2019
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 8
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 5:1294282
  OMIM Allelic Variant: 187270.0001

- Idiopathic fibrosing alveolitis, chronic form, Autosomal dominant

  ### Idiopathic fibrosing alveolitis, chronic form

  Familial pulmonary fibrosis (FPF in this GeneReview) is defined as idiopathic interstitial pneumonia (IIP) in two or more first-degree relatives (parent, sib, or offspring). Up to 20% of cases of IIP cluster in families. The clinical findings of IIP are bibasilar reticular abnormalities, ground glass opacities, or diffuse nodular lesions on high-resolution computed tomography and abnormal pulmonary function studies that include evidence of restriction (reduced VC with an increase in FEV1/FVC ratio) and/or impaired gas exchange (increased P(A-a)O2 with rest or exercise or decreased diffusion capacity of the lung for carbon monoxide [DLCO]). FPF usually presents between ages 50 and 70 years. FPF may be complicated by lung cancer; bronchoalveolar cell carcinoma, small-cell carcinoma, and adenocarcinoma have been described.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 26, 2019
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 8
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 5:1294282
  OMIM Allelic Variant: 187270.0001

- Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1, Autosomal dominant

  ### Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1

  Shortened telomeres can cause a wide variety of clinical features that constitute a phenotypic spectrum. The most severe form is dyskeratosis congenita (see, e.g., 127750), characterized by early childhood onset of skin abnormalities, bone marrow failure, predisposition to malignancy, and risk of pulmonary and hepatic fibrosis. Adult-onset pulmonary fibrosis is the most common manifestation of mutant telomerase genes. Other manifestations include aplastic anemia due to bone marrow failure, hepatic fibrosis, and increased cancer risk, particularly myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Phenotype, age at onset, and severity are determined by telomere length, not just telomerase mutation (summary by Armanios, 2009). The genetic diagnosis of telomere-related bone marrow failure and pulmonary fibrosis has implications for treatment because affected individuals generally do not respond to immunosuppression and may be at increased risk for fatal complications after bone marrow or lung transplantation (Parry et al., 2011). Genetic Heterogeneity of Telomere-Related Pulmonary Fibrosis and/or Bone Marrow Failure Also see PFBMFT2 (614743), caused by mutation in the TERC gene (602322) on chromosome 3q26; PFBMFT3 (616373), caused by mutation in the RTEL1 gene (608833) on chromosome 20q13; and PFBMFT4 (616371), caused by mutation in the PARN gene (604212) on chromosome 16p13.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 26, 2019
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 8
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 5:1294282
  OMIM Allelic Variant: 187270.0001

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 26, 2019
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 8
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 5:1294282
  OMIM Allelic Variant: 187270.0001

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 26, 2019
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 8
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 5:1294282
  OMIM Allelic Variant: 187270.0001

Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (3)

Hetero

CT

Gene: WFS1
Variant: c.1760G>A
(p.Arg587Gln)
rsID: rs71539657
Ref Allele: G
Alt Allele: A
Freq: 0.0327%rare
CADD: 13.43

ClinVar Submissions (5)

- Monogenic diabetes

  ### Monogenic diabetes

  Diabetes mellitus caused by mutation(s) in a single gene, usually presenting in childhood or early adulthood.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 29, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 5
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 4:6301555

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 29, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 5
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 4:6301555

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 29, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 5
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 4:6301555

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: COL2A1
Variant: c.3274-18C>T
rsID: rs370482993
Ref Allele: G
Alt Allele: A
Freq: 0.0334%rare
CADD: 0.562

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 14, 2018
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 12:47977173

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: IVD
Variant: c.229C>T
(p.Leu77=)
rsID: rs143807229
Ref Allele: C
Alt Allele: T
Freq: 0.0334%rare
CADD: 10.23

ClinVar Submissions (2)

- Isovaleryl-CoA dehydrogenase deficiency, Autosomal recessive

  ### Isovaleryl-CoA dehydrogenase deficiency

  Isovaleric acidemia is an inborn error of leucine metabolism caused by a deficiency of isovaleryl-CoA dehydrogenase. It can present with severe neonatal ketoacidosis leading to death, but in milder cases recurrent episodes of ketoacidosis of varying degree occur later in infancy and childhood (summary by Vockley et al., 1991).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 13, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 15:40407720

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 13, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 15:40407720

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CT

Gene: USH2A
Variant: c.14519T>C
(p.Leu4840Pro)
rsID: rs143275144
Ref Allele: A
Alt Allele: G
Freq: 0.0374%rare
CADD: 23.1

ClinVar Submissions (2)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 31, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 1:215648591

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OpenSNP
- PubMed (2)

Hetero

AG

Gene: CDAN1
Variant: c.2805-11T>A
rsID: rs200767055
Ref Allele: A
Alt Allele: T
Freq: 0.043%rare
CADD: 8.572

ClinVar Submissions (1)

- Congenital dyserythropoietic anemia

  ### Congenital dyserythropoietic anemia

  Congenital dyserythropoietic anemia (CDA) is an inherited blood disorder that affects the development of red blood cells. This disorder is one of many types of anemia, which is a condition characterized by a shortage of red blood cells. This shortage prevents the blood from carrying an adequate supply of oxygen to the body's tissues. The resulting symptoms can include tiredness (fatigue), weakness, pale skin, and other complications.Researchers have identified three major types of CDA: type I, type II, and type III. The types have different genetic causes and different but overlapping patterns of signs and symptoms.CDA type I is characterized by moderate to severe anemia. It is usually diagnosed in childhood or adolescence, although in some cases, the condition can be detected before birth. Many affected individuals have yellowing of the skin and eyes (jaundice) and an enlarged liver and spleen (hepatosplenomegaly). This condition also causes the body to absorb too much iron, which builds up and can damage tissues and organs. In particular, iron overload can lead to an abnormal heart rhythm (arrhythmia), congestive heart failure, diabetes, and chronic liver disease (cirrhosis). Rarely, people with CDA type I are born with skeletal abnormalities, most often involving the fingers and/or toes.The anemia associated with CDA type II can range from mild to severe, and most affected individuals have jaundice, hepatosplenomegaly, and the formation of hard deposits in the gallbladder called gallstones. This form of the disorder is usually diagnosed in adolescence or early adulthood. An abnormal buildup of iron typically occurs after age 20, leading to complications including heart disease, diabetes, and cirrhosis.The signs and symptoms of CDA type III tend to be milder than those of the other types. Most affected individuals do not have hepatosplenomegaly, and iron does not build up in tissues and organs. In adulthood, abnormalities of a specialized tissue at the back of the eye (the retina) can cause vision impairment. Some people with CDA type III also have a blood disorder known as monoclonal gammopathy, which can lead to a cancer of white blood cells (multiple myeloma).Several other variants of CDA have been described, although they appear to be rare and not much is known about them. Once researchers discover the genetic causes of these variants, some of them may be grouped with the three major types of CDA.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 15:42728278

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

AT

Gene: IL10RB
Variant: c.174-14T>G
rsID: rs200472684
Ref Allele: T
Alt Allele: G
Freq: 0.043%rare
CADD: 7.028

ClinVar Submissions (1)

- Inflammatory bowel disease

  ### Inflammatory bowel disease

  A spectrum of small and large bowel inflammatory diseases of unknown etiology. It includes Crohn's disease, ulcerative colitis, and colitis of indeterminate type.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 21:33276582

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

TG

Gene: NRXN1
Variant: c.*3123C>T
rsID: rs531095026
Ref Allele: G
Alt Allele: A
Freq: 0.0502%rare
CADD: 0.112

ClinVar Submissions (1)

- Pitt-Hopkins-like syndrome

  ### Pitt-Hopkins-like syndrome

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 2:49918821

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: NF2
Variant: c.*644A>G
rsID: rs75296199
Ref Allele: A
Alt Allele: G
Freq: 0.0502%rare
CADD: 0.151

ClinVar Submissions (2)

- Neurofibromatosis, type 2, Autosomal dominant

  ### Neurofibromatosis, type 2

  Neurofibromatosis 2 (NF2) is characterized by bilateral vestibular schwannomas with associated symptoms of tinnitus, hearing loss, and balance dysfunction. The average age of onset is 18 to 24 years. Almost all affected individuals develop bilateral vestibular schwannomas by age 30 years. Affected individuals may also develop schwannomas of other cranial and peripheral nerves, meningiomas, ependymomas, and, very rarely, astrocytomas. Because NF2 is considered an adult-onset disease, it may be underrecognized in children, in whom skin tumors and ocular findings (retinal hamartoma, thickened optic nerves, cortical wedge cataracts, third cranial nerve palsy) may be the first manifestations. Mononeuropathy that occurs in childhood is an increasingly recognized finding; it frequently presents as a persistent facial palsy or hand/foot drop.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 19, 2015
  Review Status: criteria provided, single submitter
  Number of Submitters: 2
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 22:29683699

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 19, 2015
  Review Status: criteria provided, single submitter
  Number of Submitters: 2
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 22:29683699

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (2)

Hetero

AG

Gene: F9
Variant: c.*293C>T
rsID: rs747670394
Ref Allele: C
Alt Allele: T
Freq: 0.0518%rare

ClinVar Submissions (1)

- Hemophilia B, Factor IX Deficiency

  ### Hemophilia B, Factor IX Deficiency

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: X:139562364

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Homo

TT

Gene: ALB
Variant: c.1446C>T
(p.Asn482=)
rsID: rs59597814
Ref Allele: C
Alt Allele: T
Freq: 0.055%rare
CADD: 2.18

ClinVar Submissions (1)

- Hyperthyroxinemia, dysalbuminemic

  ### Hyperthyroxinemia, dysalbuminemic

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 4:73418105

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CT

Gene: COL9A3
Variant: c.847-16C>T
rsID: rs188924459
Ref Allele: C
Alt Allele: T
Freq: 0.0557%rare
CADD: 12.57

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 20:62827907

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: BEST1;FTH1
Variant: c.1669G>A
(p.Glu557Lys)
rsID: rs147192139
Ref Allele: G
Alt Allele: A
Freq: 0.0581%rare
CADD: 9.825

ClinVar Submissions (3)

- Iron Overload

  ### Iron Overload

  Accumulation of iron in the tissues. It may be a manifestation of an inherited disorder (e.g., hemochromatosis) or acquired (in patients with repeated blood transfusions). Symptoms include hepatomegaly, arthritis, diabetes mellitus, and bronzed skin. If untreated it has a progressive course and may lead to death.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 11, 2016
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 11:61962823

- Retinitis Pigmentosa, Recessive

  ### Retinitis Pigmentosa, Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 11, 2016
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 11:61962823

- Vitelliform macular dystrophy type 2, Autosomal dominant

  ### Vitelliform macular dystrophy type 2

  Best vitelliform macular dystrophy is a slowly progressive macular dystrophy with onset generally in childhood and sometimes in later teenage years. Affected individuals initially have normal vision followed by decreased central visual acuity and metamorphopsia. Individuals retain normal peripheral vision and dark adaptation. Age of onset and severity of vision loss show inter- and intrafamilial variability.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 11, 2016
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 11:61962823

- Vitreoretinochoroidopathy, Autosomal dominant

  ### Vitreoretinochoroidopathy

  Autosomal dominant vitreoretinochoroidopathy (ADVIRC) is a disorder that affects several parts of the eyes, including the clear gel that fills the eye (the vitreous), the light-sensitive tissue that lines the back of the eye (the retina), and the network of blood vessels within the retina (the choroid). The eye abnormalities in ADVIRC can lead to varying degrees of vision impairment, from mild reduction to complete loss, although some people with the condition have normal vision.The signs and symptoms of ADVIRC vary, even among members of the same family. Many affected individuals have microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved. The area behind the cornea can also be abnormally small, which is described as a shallow anterior chamber. Individuals with ADVIRC can develop increased pressure in the eyes (glaucoma) or clouding of the lens of the eye (cataract). In addition, some people have breakdown (degeneration) of the vitreous or the choroid.A characteristic feature of ADVIRC, visible with a special eye exam, is a circular band of excess coloring (hyperpigmentation) in the retina. This feature can help physicians diagnose the disorder. Affected individuals may also have white spots on the retina.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 11, 2016
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 11:61962823

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 11, 2016
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 11:61962823

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed

Hetero

GA

Gene: ALPK3
Variant: c.4007C>T
(p.Ala1336Val)
rsID: rs139666355
Ref Allele: C
Alt Allele: T
Freq: 0.0733%rare
CADD: 9.12

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 01, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 15:84858139

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CT

Gene: SEC63
Variant: c.340-12_340-7delGTTTTTinsCCC
rsID: rs1554237221
Ref Allele: AAAAAC
Alt Allele: A
Freq: 0.0749%rare

ClinVar Submissions (2)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 14, 2014
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 6:107921916

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

0|1

Gene: BRCA1
Variant: c.441+36_441+50delCTTTTCTTTTTTTTT
rsID: rs1168113546
Ref Allele: AAAAAAAAAGAAAAG
Alt Allele: A
Freq: 0.0749%rare

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 25, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 17:43104072

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

0|1

Gene: G6PC3
Variant: c.566G>A
(p.Arg189Gln)
rsID: rs140294222
Ref Allele: G
Alt Allele: A
Freq: 0.0788%rare
CADD: 17.78

ClinVar Submissions (2)

- Severe congenital neutropenia 4, autosomal recessive, Autosomal recessive

  ### Severe congenital neutropenia 4, autosomal recessive

  G6PC3 deficiency is characterized by severe congenital neutropenia which occurs in a phenotypic continuum that includes the following: Isolated severe congenital neutropenia (nonsyndromic). Classic G6PC3 deficiency (severe congenital neutropenia plus cardiovascular and/or urogenital abnormalities). Severe G6PC3 deficiency (classic G6PC3 deficiency plus involvement of non-myeloid hematopoietic cell lines, additional extra-hematologic features, and pulmonary hypertension; known as Dursun syndrome). Neutropenia usually presents with recurrent bacterial infections in the first few months of life. Intrauterine growth restriction (IUGR), failure to thrive (FTT), and poor postnatal growth are common. Other findings in classic and severe G6PC3 deficiency can include inflammatory bowel disease (IBD) resembling Crohn's disease, and endocrine disorders (growth hormone deficiency, hypogonadotropic hypogonadism, and delayed puberty).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 04, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 2
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 17:44075340

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 04, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 2
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 17:44075340

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: TTN
Variant: c.1246-16G>A
rsID: rs72647847
Ref Allele: C
Alt Allele: T
Freq: 0.0796%rare
CADD: 6.779

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 19, 2014
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 2:178794567

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CT

Gene: ARHGEF15
Variant: c.1260+4G>A
rsID: rs199691980
Ref Allele: G
Alt Allele: A
Freq: 0.086%rare
CADD: 17.41

ClinVar Submissions (2)

- Early infantile epileptic encephalopathy

  ### Early infantile epileptic encephalopathy

  A neurological disorder characterized by recurring seizures presenting within the first three months of life and progressive cerebral dysfunction.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 06, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 17:8315281

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 06, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 17:8315281

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: LRRK2
Variant: c.3777+7C>T
rsID: rs41286480
Ref Allele: C
Alt Allele: T
Freq: 0.0892%rare
CADD: 0.441

ClinVar Submissions (1)

- Parkinson disease 8, autosomal dominant, Autosomal dominant

  ### Parkinson disease 8, autosomal dominant

  LRRK2-related Parkinson disease (PD) is characterized by features consistent with PD of other etiologies: initial motor features of slowly progressive asymmetric tremor at rest and/or bradykinesia, cog-wheel muscle rigidity, postural instability, and gait abnormalities that may include festination and freezing. Non-motor symptoms in LRRK2-related PD occur with similar frequency as observed in typical PD of other etiologies. Onset is generally after age 50 years.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 12:40304141

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CT

Gene: MYO5A
Variant: c.3567+19C>T
rsID: rs200875714
Ref Allele: G
Alt Allele: A
Freq: 0.09%rare
CADD: 2.09

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 15:52353852

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: TCOF1
Variant: c.3339G>A
(p.Gln1113=)
rsID: rs147074393
Ref Allele: G
Alt Allele: A
Freq: 0.094%rare
CADD: 0.128

ClinVar Submissions (1)

- Treacher Collins syndrome 1

  ### Treacher Collins syndrome 1

  Treacher Collins syndrome (TCS) is characterized by bilateral and symmetric downslanting palpebral fissures, malar hypoplasia, micrognathia, and external ear abnormalities. Hypoplasia of the zygomatic bones and mandible can cause significant feeding and respiratory difficulties. About 40%-50% of individuals have conductive hearing loss attributed most commonly to malformation of the ossicles and hypoplasia of the middle ear cavities. Inner ear structures tend to be normal. Other, less common abnormalities include cleft palate and unilateral or bilateral choanal stenosis or atresia. Typically intellect is normal.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 28, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 5:150391998

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GA

Gene: KIF21A
Variant: c.3602C>G
(p.Pro1201Arg)
rsID: rs149075970
Ref Allele: G
Alt Allele: C
Freq: 0.0948%rare
CADD: 23.2

ClinVar Submissions (1)

- Congenital fibrosis of the extraocular muscles

  ### Congenital fibrosis of the extraocular muscles

  Congenital fibrosis of the extraocular muscles (CFEOM) refers to at least eight genetically defined strabismus syndromes (CFEOM1A, CFEOM1B, CFEOM2, CFEOM3A, CFEOM3B, CFEOM3C, Tukel syndrome, and CFEOM3 with polymicrogyria) characterized by congenital non-progressive ophthalmoplegia (inability to move the eyes) with or without ptosis (droopy eyelids) affecting part or all of the oculomotor nucleus and nerve (cranial nerve III) and its innervated muscles (superior, medial, and inferior recti, inferior oblique, and levator palpabrae superioris) and/or the trochlear nucleus and nerve (cranial nerve IV) and its innervated muscle (the superior oblique). In general, affected individuals have severe limitation of vertical gaze (usually upgaze) and variable limitation of horizontal gaze. Individuals with CFEOM frequently compensate for the ophthalmoplegia by maintaining abnormal head positions at rest and by moving their heads rather than their eyes to track objects. Individuals with CFEOM3A may also have intellectual disability, social disability, Kallmann syndrome, facial weakness, and vocal cord paralysis; and/or may develop a progressive sensorimotor axonal polyneuropathy. Individuals with Tukel syndrome also have postaxial oligodactyly or oligosyndactyly of the hands. Those with CFEOM3 with polymicrogyria also have microcephaly and intellectual disability.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 12:39322698

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GC

Gene: LAMA3
Variant: c.30C>T
(p.Cys10=)
rsID: rs145044428
Ref Allele: C
Alt Allele: T
Freq: 0.0948%rare
CADD: 6.394

ClinVar Submissions (1)

- Epidermolysis bullosa, junctional

  ### Epidermolysis bullosa, junctional

  Junctional epidermolysis bullosa (JEB) is characterized by fragility of the skin and mucous membranes, manifest by blistering with little or no trauma. Blistering may be severe and granulation tissue can form on the skin around the oral and nasal cavities, fingers and toes, and internally around the upper airway. Blisters generally heal with no significant scarring. Broad classification of JEB includes JEB generalized severe and JEB generalized intermediate. In JEB generalized severe, blisters are present at birth or become apparent in the neonatal period. Congenital malformations of the urinary tract and bladder may also occur. In JEB generalized intermediate, the phenotype may be mild with blistering localized to hands, feet, knees, and elbows with or without renal or ureteral involvement. Some individuals never blister after the newborn period. Additional features shared by JEB and the other major forms of epidermolysis bullosa (EB) include congenital localized absence of skin (aplasia cutis congenita), milia, nail dystrophy, scarring alopecia, hypotrichosis, pseudosyndactyly, and other contractures.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 18:23873074

- Laryngoonychocutaneous syndrome, Autosomal recessive

  ### Laryngoonychocutaneous syndrome

  Laryngo-onycho-cutaneous (LOC) syndrome is a disorder that leads to abnormalities of the voicebox (laryngo-), finger- and toenails (onycho-), and skin (cutaneous). Many of the condition's signs and symptoms are related to the abnormal growth of granulation tissue in different parts of the body. This red, bumpy tissue is normally produced during wound healing and is usually replaced by skin cells as healing continues. However, in people with LOC syndrome, this tissue grows even when there is no major injury.One of the first symptoms in infants with LOC syndrome is a hoarse cry due to ulcers or overgrowth of granulation tissue in the voicebox (the larynx). Excess granulation tissue can also block the airways, leading to life-threatening breathing problems; as a result many affected individuals do not survive past childhood.In LOC syndrome, granulation tissue also grows in the eyes, specifically the conjunctiva, which are the moist tissues that line the eyelids and the white part of the eyes. Affected individuals often have impairment or complete loss of vision due to the tissue overgrowth.Another common feature of LOC syndrome is missing patches of skin (cutaneous erosions). The erosions heal slowly and may become infected. People with LOC syndrome can also have malformed nails and small, abnormal teeth. The hard, white material that forms the protective outer layer of each tooth (enamel) is thin, which contributes to frequent cavities.LOC syndrome is typically considered a subtype of another skin condition called junctional epidermolysis bullosa, which is characterized by fragile skin that blisters easily. While individuals with junctional epidermolysis bullosa can have some of the features of LOC syndrome, they do not usually have overgrowth of granulation tissue in the conjunctiva.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 18:23873074

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CT

Gene: CCDC50
Variant: c.617C>T
(p.Ser206Phe)
rsID: rs138153104
Ref Allele: C
Alt Allele: T
Freq: 0.0956%rare
CADD: 22.3

ClinVar Submissions (2)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 23, 2016
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 2
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 3:191375230

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: MYH9
Variant: c.1158C>T
(p.Thr386=)
rsID: rs138502859
Ref Allele: G
Alt Allele: A
Freq: 0.0995%rare
CADD: 11.44

ClinVar Submissions (4)

- MYH9-related disorder

  ### MYH9-related disorder

  An autosomal dominant disorder characterized by the triad of thrombocytopenia, giant platelets, and characteristic inclusions in peripheral blood leukocytes, without other organ dysfunction; it is associated with mutation of the MYH9 gene.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 25, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 22:36318276

- Nonsyndromic Hearing Loss, Dominant

  ### Nonsyndromic Hearing Loss, Dominant

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 25, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 22:36318276

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 25, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 22:36318276

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (2)

Hetero

GA

Gene: CHST3
Variant: c.*4450G>C
rsID: rs183731077
Ref Allele: G
Alt Allele: C
Freq: 0.1011%rare
CADD: 8.174

ClinVar Submissions (1)

- Larsen syndrome, Autosomal dominant

  ### Larsen syndrome

  Larsen syndrome is a disorder that affects the development of bones throughout the body. The signs and symptoms of Larsen syndrome vary widely even within the same family. Affected individuals are usually born with inward- and upward-turning feet (clubfeet) and dislocations of the hips, knees, and elbows. They generally have small extra bones in their wrists and ankles that are visible on x-ray images. The tips of their fingers, especially the thumbs, are typically blunt and square-shaped (spatulate).People with Larsen syndrome may also have an unusually large range of joint movement (hypermobility) and short stature. They can also have abnormal curvature of the spine (kyphosis or scoliosis) that may compress the spinal cord and lead to weakness of the limbs.Characteristic facial features include a prominent forehead (frontal bossing), flattening of the bridge of the nose and of the middle of the face (midface hypoplasia), and wide-set eyes (ocular hypertelorism). Some people with Larsen syndrome have an opening in the roof of the mouth (a cleft palate) or hearing loss caused by malformations in the tiny bones in the ears (ossicles). Some affected individuals experience respiratory problems as a result of weakness of the airways that can lead to partial closing, short pauses in breathing (apnea), and frequent respiratory infections. People with Larsen syndrome can survive into adulthood and intelligence is unaffected.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 10:72012921

- Skeletal dysplasia

  ### Skeletal dysplasia

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 10:72012921

- Spondyloepiphyseal dysplasia, Autosomal dominant

  ### Spondyloepiphyseal dysplasia

  Spondyloepiphyseal dysplasia congenita is an autosomal dominant chondrodysplasia characterized by disproportionate short stature (short trunk), abnormal epiphyses, and flattened vertebral bodies. Skeletal features are manifested at birth and evolve with time. Other features include myopia and/or retinal degeneration with retinal detachment and cleft palate (summary by Anderson et al., 1990).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 10:72012921

- Spondyloepiphyseal dysplasia with congenital joint dislocations

  ### Spondyloepiphyseal dysplasia with congenital joint dislocations

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 10:72012921

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GC

Gene: CHST3
Variant: c.*1184C>G
rsID: rs187692473
Ref Allele: C
Alt Allele: G
Freq: 0.1059%rare
CADD: 0.933

ClinVar Submissions (1)

- Larsen syndrome, Autosomal dominant

  ### Larsen syndrome

  Larsen syndrome is a disorder that affects the development of bones throughout the body. The signs and symptoms of Larsen syndrome vary widely even within the same family. Affected individuals are usually born with inward- and upward-turning feet (clubfeet) and dislocations of the hips, knees, and elbows. They generally have small extra bones in their wrists and ankles that are visible on x-ray images. The tips of their fingers, especially the thumbs, are typically blunt and square-shaped (spatulate).People with Larsen syndrome may also have an unusually large range of joint movement (hypermobility) and short stature. They can also have abnormal curvature of the spine (kyphosis or scoliosis) that may compress the spinal cord and lead to weakness of the limbs.Characteristic facial features include a prominent forehead (frontal bossing), flattening of the bridge of the nose and of the middle of the face (midface hypoplasia), and wide-set eyes (ocular hypertelorism). Some people with Larsen syndrome have an opening in the roof of the mouth (a cleft palate) or hearing loss caused by malformations in the tiny bones in the ears (ossicles). Some affected individuals experience respiratory problems as a result of weakness of the airways that can lead to partial closing, short pauses in breathing (apnea), and frequent respiratory infections. People with Larsen syndrome can survive into adulthood and intelligence is unaffected.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 10:72009655

- Skeletal dysplasia

  ### Skeletal dysplasia

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 10:72009655

- Spondyloepiphyseal dysplasia, Autosomal dominant

  ### Spondyloepiphyseal dysplasia

  Spondyloepiphyseal dysplasia congenita is an autosomal dominant chondrodysplasia characterized by disproportionate short stature (short trunk), abnormal epiphyses, and flattened vertebral bodies. Skeletal features are manifested at birth and evolve with time. Other features include myopia and/or retinal degeneration with retinal detachment and cleft palate (summary by Anderson et al., 1990).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 10:72009655

- Spondyloepiphyseal dysplasia with congenital joint dislocations

  ### Spondyloepiphyseal dysplasia with congenital joint dislocations

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 10:72009655

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CG

Gene: NEB
Variant: c.25140C>T
(p.Asp8380=)
rsID: rs201825451
Ref Allele: G
Alt Allele: A
Freq: 0.1067%rare
CADD: 17.49

ClinVar Submissions (5)

- Nemaline Myopathy, Recessive

  ### Nemaline Myopathy, Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 08, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 5
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 2:151492120

- Nemaline myopathy 2, Autosomal recessive

  ### Nemaline myopathy 2

  Nemaline myopathy (referred to in this entry as NM) is characterized by weakness, hypotonia, and depressed or absent deep tendon reflexes. Muscle weakness is usually most severe in the face, the neck flexors, and the proximal limb muscles. The clinical classification defines six forms of NM, which are classified by onset and severity of motor and respiratory involvement: Severe congenital (neonatal) (16% of all individuals with NM). Amish NM. Intermediate congenital (20%). Typical congenital (46%). Childhood-onset (13%). Adult-onset (late-onset) (4%). Considerable overlap occurs among the forms. There are significant differences in survival between individuals classified as having severe, intermediate, and typical congenital NM. Severe neonatal respiratory disease and the presence of arthrogryposis multiplex congenita are associated with death in the first year of life. Independent ambulation before age 18 months is predictive of survival. Most children with typical congenital NM are eventually able to walk.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 08, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 5
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 2:151492120

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 08, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 5
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 2:151492120

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 08, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 5
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 2:151492120

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (2)

Hetero

GA

Gene: LOXHD1
Variant: c.3340G>A
(p.Gly1114Arg)
rsID: rs142931455
Ref Allele: C
Alt Allele: T
Freq: 0.1123%rare
CADD: 13.67

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 25, 2015
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 18:46477188

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: FYCO1
Variant: c.1142C>T
(p.Thr381Met)
rsID: rs3733101
Ref Allele: G
Alt Allele: A
Freq: 0.1147%rare
CADD: 1.983

ClinVar Submissions (1)

- Congenital cataract

  ### Congenital cataract

  A congenital cataract.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 3:45968192

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OpenSNP
- PubMed

Hetero

GA

Gene: LDLR
Variant: c.694+25C>T
rsID: rs199540175
Ref Allele: C
Alt Allele: T
Freq: 0.1155%rare
CADD: 0.081

ClinVar Submissions (4)

- Familial hypercholesterolemia, Autosomal dominant

  ### Familial hypercholesterolemia

  Familial hypercholesterolemia (FH) is characterized by severely elevated LDL cholesterol (LDL-C) levels that lead to atherosclerotic plaque deposition in the coronary arteries and proximal aorta at an early age, leading to an increased risk for cardiovascular disease. Xanthomas (patches of yellowish cholesterol buildup) may worsen with age as a result of extremely high cholesterol levels. Xanthomas can occur around the eyelids and within the tendons of the elbows, hands, knees, and feet. In FH, the more common cardiovascular disease is coronary artery disease (CAD), which may manifest as angina and myocardial infarction; stroke occurs more rarely. Untreated men are at a 50% risk for a fatal or non-fatal coronary event by age 50 years; untreated women are at a 30% risk by age 60 years. An estimated 70%-95% of FH results from a heterozygous pathogenic variant in one of three genes (APOB, LDLR, PCSK9). FH is the most common inherited cardiovascular disease, with a prevalence of 1:200-250. FH likely accounts for 2%-3% of myocardial infarctions in individuals younger than age 60 years. In contrast, homozygous FH (HoFH) results from biallelic (homozygous or compound heterozygous) pathogenic variants in one of these known genes (APOB, LDLR, PCSK9). Most individuals with HoFH experience severe CAD by their mid-20s and the rate of either death or coronary bypass surgery by the teenage years is high. Severe aortic stenosis is also common.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 14, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 4
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 19:11105625

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 14, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 4
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 19:11105625

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (3)

Hetero

CT

Gene: C3
Variant: c.2067G>A
(p.Glu689=)
rsID: rs147477257
Ref Allele: C
Alt Allele: T
Freq: 0.1163%rare
CADD: 8.61

ClinVar Submissions (1)

- Atypical hemolytic uremic syndrome

  ### Atypical hemolytic uremic syndrome

  Hemolytic-uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia, and renal failure caused by platelet thrombi in the microcirculation of the kidney and other organs. The onset of atypical HUS (aHUS) ranges from the neonatal period to adulthood. Genetic aHUS accounts for an estimated 60% of all aHUS. Individuals with genetic aHUS frequently experience relapse even after complete recovery following the presenting episode; 60% of genetic aHUS progresses to end-stage renal disease (ESRD).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 19:6707254

- C3 deficiency

  ### C3 deficiency

  A rare genetic disorder with an autosomal recessive pattern of inheritance. It is caused by the ineffective or decreased biosynthesis of the third complement component, C3. C3 deficiency may also be acquired acutely post-infection or chronically from co-morbid autoimmune disorders. If C3 is adequately synthesized, its rapid depletion may result in a functional deficiency. Clinical signs of the inherited deficiency present within the first decade of life and are consistent with the signs of recurrent systemic infection or immune complex disease. Deficiency of serum C3 and its major cleavage product, C3b, will decrease the effective humoral immune response to encapsulated bacteria. Deficiency of C3 also impairs clearance of circulating immune complexes and therefore predisposes to rheumatic and renal disease.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 19:6707254

- Macular degeneration

  ### Macular degeneration

  A nonspecific term denoting degeneration of the retinal pigment epithelium and/or retinal photoreceptor cells of the macula lutea.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 19:6707254

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CT

Gene: SLC46A1
Variant: c.*1332G>A
rsID: rs146041886
Ref Allele: C
Alt Allele: T
Freq: 0.1266%rare
CADD: 2.161

ClinVar Submissions (1)

- Congenital defect of folate absorption, Autosomal recessive

  ### Congenital defect of folate absorption

  Hereditary folate malabsorption (HFM) is characterized by folate deficiency with impaired intestinal folate absorption and impaired folate transport into the central nervous system. Findings include poor feeding, failure to thrive, and anemia. There can be leukopenia and thrombocytopenia, diarrhea and/or oral mucositis, hypoimmunoglobulinemia, and other immunologic dysfunction resulting in infections, most often Pneumocystis jerovicii pneumonia. Neurologic manifestations include developmental delays, cognitive and motor impairment, behavioral disorders and, frequently, seizures.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 17:28398324

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CT

Gene: SLC1A3
Variant: c.*1206G>A
rsID: rs530235885
Ref Allele: G
Alt Allele: A
Freq: 0.1322%rare
CADD: 0.323

ClinVar Submissions (1)

- Episodic ataxia

  ### Episodic ataxia

  Periodic spells of incoordination and imbalance, that is, episodes of ataxia typically lasting from 10 minutes to several hours or days.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:36687475

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: CPA6
Variant: c.619C>G
(p.Gln207Glu)
rsID: rs35993949
Ref Allele: G
Alt Allele: C
Freq: 0.1354%rare
CADD: 26.7

ClinVar Submissions (7)

- Epilepsy, familial temporal lobe, 5, Autosomal dominant

  ### Epilepsy, familial temporal lobe, 5

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 25, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 7
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 8:67506804
  OMIM Allelic Variant: 609562.0003

- Febrile seizures, familial, 11, Autosomal recessive

  ### Febrile seizures, familial, 11

  Familial febrile seizures-11 is an autosomal recessive seizure disorder characterized by early childhood onset of simple or complex seizures associated with fever. These seizures usually remit later in childhood with no neurologic sequelae (summary by Salzmann et al., 2012). For a general description and a discussion of genetic heterogeneity of familial febrile seizures, see FEB1 (121210).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 25, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 7
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 8:67506804
  OMIM Allelic Variant: 609562.0003

- Global developmental delay

  ### Global developmental delay

  A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age. [DDD:hvfirth, HPO:sdoelken]

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 25, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 7
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 8:67506804
  OMIM Allelic Variant: 609562.0003

- Rolandic epilepsy

  ### Rolandic epilepsy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 25, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 7
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 8:67506804
  OMIM Allelic Variant: 609562.0003

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 25, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 7
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 8:67506804
  OMIM Allelic Variant: 609562.0003

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 25, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 7
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 8:67506804
  OMIM Allelic Variant: 609562.0003

Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (2)

Hetero

GC

Gene: PRICKLE1
Variant: c.177C>T
(p.Tyr59=)
rsID: rs144843013
Ref Allele: G
Alt Allele: A
Freq: 0.1394%rare
CADD: 13.96

ClinVar Submissions (6)

- Progressive myoclonus epilepsy with ataxia, Autosomal recessive

  ### Progressive myoclonus epilepsy with ataxia

  PRICKLE1-related progressive myoclonus epilepsy (PME) with ataxia is characterized by myoclonic seizures (lightning-like jerks), generalized convulsive seizures, varying degrees of neurologic decline especially manifest as ataxia, and normal intellectual abilities. Onset of symptoms is between ages five and ten years. Action myoclonus may affect the limbs or bulbar muscles, sometimes with spontaneous myoclonus of facial muscles. Marked dysarthria may occur. Seizures can be myoclonic or tonic-clonic and are often nocturnal.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 10, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 6
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 12:42470315

- Seizures

  ### Seizures

  Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or "seizure disorder."

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 10, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 6
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 12:42470315

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 10, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 6
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 12:42470315

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GA

Gene: CNTN1
Variant: c.2980+19A>T
rsID: rs181426756
Ref Allele: A
Alt Allele: T
Freq: 0.1449%rare
CADD: 6.657

ClinVar Submissions (2)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 22, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 12:41029238

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

AT

Gene: WT1
Variant: c.*1239T>A
rsID: rs534396876
Ref Allele: A
Alt Allele: T
Freq: 0.1481%rare
CADD: 17.01

ClinVar Submissions (1)

- Diffuse mesangial sclerosis, Autosomal dominant

  ### Diffuse mesangial sclerosis

  Nephrotic syndrome, a malfunction of the glomerular filter, leads to proteinuria, edema, and, in steroid-resistant nephrotic syndrome, end-stage renal disease (ESRD). Renal histopathology in NPHS4 due to WT1 mutations most often shows diffuse mesangial sclerosis (DMS), but can also show focal segmental glomerulosclerosis (FSGS). Both of these terms refer to pathologic findings and may be associated with the same clinical phenotype, namely nephrotic syndrome (review by Schumacher et al., 1998). For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome, see NPHS1 (256300).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:32387819

- Meacham syndrome

  ### Meacham syndrome

  A multiple malformation syndrome with characteristics of congenital diaphragmatic abnormalities, genital defects and cardiac malformations. Less than 15 patients have been reported worldwide. Ambiguous or female external genitalia are present in individuals with 46,XY karyotype. The genital abnormalities are variable and may include a true double vagina or septate vagina, absent uterus, abnormal male gonads in the presence of normal external female genitalia or male pseudohermaphroditism with abnormal internal female genitalia. Complex cyanotic congenital heart defects, (hypoplastic right lungs, anomalous pulmonary venous return and abnormalities of the diaphragm) are frequent. One patient with rhabdomyomatous dysplasia of the lungs has been reported. Mutations in the WT1 gene have been identified in some patients with Meacham syndrome. All patients reported to date died in early childhood.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:32387819

- Wilms Tumor

  ### Wilms Tumor

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:32387819

- Wilms tumor, aniridia, genitourinary anomalies, and mental retardation syndrome, Autosomal dominant

  ### Wilms tumor, aniridia, genitourinary anomalies, and mental retardation syndrome

  PAX6-related aniridia occurs either as an isolated ocular abnormality or as part of the Wilms tumor-aniridia-genital anomalies-retardation (WAGR) syndrome. Aniridia is a pan ocular disorder affecting the cornea, iris, intraocular pressure (resulting in glaucoma), lens (cataract and lens subluxation), fovea (foveal hypoplasia), and optic nerve (optic nerve coloboma and hypoplasia). Individuals with aniridia characteristically show nystagmus and impaired visual acuity (usually 20/100 - 20/200); however, milder forms of aniridia with subtle iris architecture changes, good vision, and normal foveal structure do occur. Other ocular involvement may include strabismus and occasionally microphthalmia. Although the severity of aniridia can vary between and within families, little variability is usually observed in the two eyes of an affected individual. WAGR syndrome. The risk for Wilms tumor is 42.5%-77%; of those who develop Wilms tumor, 90% do so by age four years and 98% by age seven years. Genital anomalies in males can include cryptorchidism and hypospadias (sometimes resulting in ambiguous genitalia), urethral strictures, ureteric abnormalities, and gonadoblastoma. While females typically have normal external genitalia, they may have uterine abnormalities and streak ovaries. Intellectual disability (defined as IQ <74) is observed in 70%; behavioral abnormalities include attention deficit hyperactivity disorder (ADHD), autism spectrum disorder, anxiety, depression, and obsessive-compulsive disorder. Other individuals with WAGR syndrome can have normal intellect without behavioral problems.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:32387819

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

AT

Gene: OTOF
Variant: c.4980C>T
(p.Asp1660=)
rsID: rs149549554
Ref Allele: G
Alt Allele: A
Freq: 0.1609%rare
CADD: 0.009

ClinVar Submissions (2)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 01, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:26464087

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: FASTKD2
Variant: c.*2431C>G
rsID: rs146898986
Ref Allele: C
Alt Allele: G
Freq: 0.1625%rare
CADD: 11.3

ClinVar Submissions (1)

- Hepatic failure, early-onset, and neurologic disorder due to cytochrome C oxidase deficiency, Autosomal recessive

  ### Hepatic failure, early-onset, and neurologic disorder due to cytochrome C oxidase deficiency

  Leigh syndrome (or subacute necrotizing encephalomyelopathy) is characterized by decompensation (often with elevated lactate levels in blood and/or CSF) during an intercurrent illness. It is typically associated with psychomotor retardation or regression, often followed by transient or prolonged stabilization or even improvement, but inevitably resulting in eventual progressive neurologic decline, typically occurring in stepwise decrements. Neurologic manifestations include hypotonia, spasticity, movement disorders (including chorea), cerebellar ataxia, and peripheral neuropathy. Extraneurologic manifestations may include hypertrophic cardiomyopathy, hypertrichosis, anemia, renal tubulopathy, liver involvement, ptosis, and muscle weakness. Onset is typically between ages three and 12 months; about 50% of affected individuals die by age three years, most often as a result of respiratory or cardiac failure. Later onset (including in adulthood) and long-term survival may occasionally occur.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 2:206794233

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CG

Gene: DHCR24
Variant: c.*2554C>T
rsID: rs144220338
Ref Allele: G
Alt Allele: A
Freq: 0.1633%rare
CADD: 2.815

ClinVar Submissions (1)

- Desmosterolosis, Autosomal recessive

  ### Desmosterolosis

  Desmosterolosis is a rare autosomal recessive disorder characterized by multiple congenital anomalies and elevated levels of the cholesterol precursor desmosterol in plasma, tissue, and cultured cells (summary by Waterham et al., 2001).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 1:54849679

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GA

Gene: AIRE
Variant: c.1567-5C>T
rsID: rs192215705
Ref Allele: C
Alt Allele: T
Freq: 0.1848%rare
CADD: 3.727

ClinVar Submissions (4)

- Polyglandular autoimmune syndrome, type 1, Autosomal dominant

  ### Polyglandular autoimmune syndrome, type 1

  Autoimmune polyglandular syndrome type I is characterized by the presence of 2 of 3 major clinical symptoms: Addison disease, and/or hypoparathyroidism, and/or chronic mucocutaneous candidiasis (Neufeld et al., 1981).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 26, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 21:44297651

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 26, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 21:44297651

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: PKHD1
Variant: c.652G>A
(p.Glu218Lys)
rsID: rs149522482
Ref Allele: C
Alt Allele: T
Freq: 0.1903%rare
CADD: 22.3

ClinVar Submissions (3)

- Autosomal recessive polycystic kidney disease, Autosomal recessive

  ### Autosomal recessive polycystic kidney disease

  Autosomal recessive polycystic kidney disease (ARPKD) belongs to a group of congenital hepatorenal fibrocystic syndromes and is a cause of significant renal and liver-related morbidity and mortality in children. The majority of individuals with ARPKD present in the neonatal period with enlarged echogenic kidneys. Renal disease is characterized by nephromegaly, hypertension, and varying degrees of renal dysfunction. More than 50% of affected individuals with ARPKD progress to end-stage renal disease (ESRD) within the first decade of life; ESRD may require kidney transplantation. Pulmonary hypoplasia resulting from oligohydramnios occurs in a number of affected infants. Approximately 30% of these infants die in the neonatal period or within the first year of life from respiratory insufficiency or superimposed pulmonary infections. With neonatal respiratory support and renal replacement therapies, the long-term survival of these infants has improved to greater than 80%. As advances in renal replacement therapy and kidney transplantation improve long-term survival, it is likely that clinical hepatobiliary disease will become a major feature of the natural history of ARPKD. In addition, a subset of individuals with this disorder are identified with hepatosplenomegaly; the renal disease is often mild and may be discovered incidentally during imaging studies of the abdomen. Approximately 50% of infants will have clinical evidence of liver involvement at diagnosis although histologic hepatic fibrosis is invariably present at birth. This can lead to progressive portal hypertension with resulting esophageal or gastric varices, enlarged hemorrhoids, splenomegaly, hypersplenism, protein-losing enteropathy, and gastrointestinal bleeding. Other hepatic findings include nonobstructed dilatation of the intrahepatic bile ducts (Caroli syndrome) and dilatation of the common bile duct, which may lead to recurrent or persistent bacterial ascending cholangitis due to dilated bile ducts and stagnant bile flow. An increasing number of affected individuals surviving the neonatal period will eventually require portosystemic shunting or liver transplantation for complications of portal hypertension or cholangitis. The classic neonatal presentation of ARPKD notwithstanding, there is significant variability in age and presenting clinical symptoms related to the relative degree of renal and biliary abnormalities.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 18, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 6:52071021

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 18, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 6:52071021

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed

Hetero

CT

Gene: ANO5
Variant: c.*1967G>A
rsID: rs147606218
Ref Allele: G
Alt Allele: A
Freq: 0.1935%rare
CADD: 0.652

ClinVar Submissions (1)

- Limb-Girdle Muscular Dystrophy, Recessive

  ### Limb-Girdle Muscular Dystrophy, Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 11:22281732

- Miyoshi myopathy

  ### Miyoshi myopathy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 11:22281732

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: HERC2
Variant: c.2389A>G
(p.Met797Val)
rsID: rs150930758
Ref Allele: T
Alt Allele: C
Freq: 0.1975%rare
CADD: 4.777

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 21, 2015
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 15:28257189

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

TC

Gene: RIMS1
Variant: c.*283A>G
rsID: rs140634975
Ref Allele: A
Alt Allele: G
Freq: 0.2047%rare
CADD: 0.775

ClinVar Submissions (1)

- Cone-Rod Dystrophy, Dominant

  ### Cone-Rod Dystrophy, Dominant

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 6:72400997

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

AG

Gene: MYBPC3
Variant: c.565G>A
(p.Val189Ile)
rsID: rs11570052
Ref Allele: C
Alt Allele: T
Freq: 0.2071%rare
CADD: 17.18

ClinVar Submissions (9)

- Cardiovascular phenotype

  ### Cardiovascular phenotype

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 29, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:47349863

- Familial hypertrophic cardiomyopathy 4, Autosomal dominant

  ### Familial hypertrophic cardiomyopathy 4

  Hypertrophic cardiomyopathy (HCM) is typically defined by the presence of unexplained left ventricular hypertrophy (LVH). Such LVH occurs in a non-dilated ventricle in the absence of other cardiac or systemic disease capable of producing the observed magnitude of increased LV wall thickness, such as pressure overload (e.g., long-standing hypertension, aortic stenosis) or storage/infiltrative disorders (e.g., Fabry disease, amyloidosis). The clinical manifestations of HCM range from asymptomatic LVH to progressive heart failure to sudden cardiac death (SCD), and vary from individual to individual even within the same family. Common symptoms include shortness of breath (particularly with exertion), chest pain, palpitations, orthostasis, presyncope, and syncope. Most often the LVH of HCM becomes apparent during adolescence or young adulthood, although it may also develop late in life, in infancy, or in childhood.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 29, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:47349863

- Hypertrophic cardiomyopathy

  ### Hypertrophic cardiomyopathy

  A condition in which the myocardium is hypertrophied without an obvious cause. The hypertrophy is generally asymmetric and may be associated with obstruction of the ventricular outflow tract.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 29, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:47349863

- Primary familial hypertrophic cardiomyopathy

  ### Primary familial hypertrophic cardiomyopathy

  Hypertrophic cardiomyopathy (HCM) is typically defined by the presence of unexplained left ventricular hypertrophy (LVH). Such LVH occurs in a non-dilated ventricle in the absence of other cardiac or systemic disease capable of producing the observed magnitude of increased LV wall thickness, such as pressure overload (e.g., long-standing hypertension, aortic stenosis) or storage/infiltrative disorders (e.g., Fabry disease, amyloidosis). The clinical manifestations of HCM range from asymptomatic LVH to progressive heart failure to sudden cardiac death (SCD), and vary from individual to individual even within the same family. Common symptoms include shortness of breath (particularly with exertion), chest pain, palpitations, orthostasis, presyncope, and syncope. Most often the LVH of HCM becomes apparent during adolescence or young adulthood, although it may also develop late in life, in infancy, or in childhood.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 29, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:47349863

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 29, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:47349863

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 29, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:47349863

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (5)

Hetero

CT

Gene: FYCO1
Variant: c.1474C>T
(p.Arg492Trp)
rsID: rs143704916
Ref Allele: G
Alt Allele: A
Freq: 0.219%rare
CADD: 15.62

ClinVar Submissions (2)

- Cataract, autosomal recessive congenital 2, Autosomal recessive

  ### Cataract, autosomal recessive congenital 2

  Mutations in the FYCO1 gene have been identified in families with autosomal recessive cataract described as congenital and congenital nuclear. The preferred title/symbol of this entry was formerly 'Cataract, Autosomal Recessive Congenital 2; CATC2.'

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 19, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 2
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 3:45967860

- Congenital cataract

  ### Congenital cataract

  A congenital cataract.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 19, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 2
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 3:45967860

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GA

Gene: IFT122
Variant: c.3282C>T
(p.Arg1094=)
rsID: rs76881473
Ref Allele: C
Alt Allele: T
Freq: 0.2254%rare
CADD: 0.214

ClinVar Submissions (2)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 02, 2016
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 2
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 3:129514530

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: ZBTB24
Variant: c.1672G>A
(p.Asp558Asn)
rsID: rs61731736
Ref Allele: C
Alt Allele: T
Freq: 0.2286%rare
CADD: 20.9

ClinVar Submissions (1)

- Immunodeficiency-centromeric instability-facial anomalies syndrome 2, Autosomal recessive

  ### Immunodeficiency-centromeric instability-facial anomalies syndrome 2

  Immunodeficiency, centromeric instability, and facial dysmorphism (ICF) syndrome is a rare autosomal recessive disorder characterized by facial dysmorphism, immunoglobulin deficiency resulting in recurrent infections, and mental retardation. Laboratory studies of patient cells show hypomethylation of satellite regions of chromosomes 1, 9, and 16, as well as pericentromeric chromosomal instability in response to phytohemagglutinin stimulation (summary by de Greef et al., 2011). For a discussion of genetic heterogeneity of immunodeficiency-centromeric instability-facial anomalies syndrome, see ICF1 (242860).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 21, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 6:109466273

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CT

Gene: KMT2C
Variant: c.10763C>T
(p.Ser3588Leu)
rsID: rs148585727
Ref Allele: G
Alt Allele: A
Freq: 0.2294%rare
CADD: 26.7

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 19, 2013
  Review Status: no assertion provided
  Number of Submitters: 1
  Clinical Significance: not provided
  Assembly: GRCh38
  Chromosome/Position: 7:152162814

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: PLOD3
Variant: c.1935+105T>G
rsID: rs186082235
Ref Allele: A
Alt Allele: C
Freq: 0.2333%rare
CADD: 0.944

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 19, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 7:101207473

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

AC

Gene: TRIOBP
Variant: c.2149C>G
(p.Gln717Glu)
rsID: rs186620158
Ref Allele: C
Alt Allele: G
Freq: 0.2333%rare
CADD: 0.359

ClinVar Submissions (2)

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 14, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 22:37724705

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 14, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 22:37724705

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CG

Gene: ADGRG1
Variant: c.1017+8G>A
rsID: rs186479054
Ref Allele: G
Alt Allele: A
Freq: 0.2341%rare
CADD: 0.702

ClinVar Submissions (4)

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 09, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 16:57656000

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 09, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 16:57656000

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: SERPINA6
Variant: c.344T>A
(p.Leu115His)
rsID: rs113418909
Ref Allele: A
Alt Allele: T
Freq: 0.2357%rare
CADD: 24.7

ClinVar Submissions (2)

- Corticosteroid-binding globulin deficiency, Autosomal dominant

  ### Corticosteroid-binding globulin deficiency

  Corticosteroid-binding globulin deficiency is a condition with subtle signs and symptoms, the most frequent being extreme tiredness (fatigue), especially after physical exertion. Many people with this condition have unusually low blood pressure (hypotension). Some affected individuals have a fatty liver or experience chronic pain, particularly in their muscles. These features vary among affected individuals, even those within the same family.Many people with corticosteroid-binding globulin deficiency have only one or two of these features; others have no signs and symptoms of the disorder and are only diagnosed after a relative is found to be affected.Some people with corticosteroid-binding globulin deficiency also have a condition called chronic fatigue syndrome. The features of chronic fatigue syndrome are prolonged fatigue that interferes with daily activities, as well as general symptoms, such as sore throat or headaches.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 08, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 2
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 14:94314305
  OMIM Allelic Variant: 122500.0001

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 08, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 2
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 14:94314305
  OMIM Allelic Variant: 122500.0001

Moderate clinical importance, Uncertain pathogenic — Reported to cause corticosteroid deficiency in a recessive fashion, a disease which can cause fatigue after exertion. This variant was reported by Van Baelen et al 1982 (PMID: 7061486), and recorded in ClinVar by OMIM (http://www.ncbi.nlm.nih.gov/clinvar/RCV000018495/). Van Baelen et al described this variant as "transcortin Leuven", who reported the variant protein product had 3.6-fold reduced affinity for cortisol at 28C.

Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (2)

Hetero

AT

Gene: LIPA
Variant: c.-71C>A
rsID: rs553435176
Ref Allele: G
Alt Allele: T
Freq: 0.2445%rare
CADD: 2.096

ClinVar Submissions (1)

- Wolman disease

  ### Wolman disease

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 10:89251806

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GT

Gene: PCNT
Variant: c.9274-3C>T
rsID: rs200348425
Ref Allele: C
Alt Allele: T
Freq: 0.2477%rare
CADD: 12.85

ClinVar Submissions (4)

- Microcephalic Osteodysplastic Primordial Dwarfism

  ### Microcephalic Osteodysplastic Primordial Dwarfism

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 25, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 21:46440080

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 25, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 21:46440080

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: MYH3
Variant: c.2926-8C>T
rsID: rs188588330
Ref Allele: G
Alt Allele: A
Freq: 0.2501%rare
CADD: 8.792

ClinVar Submissions (2)

- Arthrogryposis multiplex congenita

  ### Arthrogryposis multiplex congenita

  A non-progressive finding characterized by multiple joint contractures found throughout the body at birth.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 2
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 17:10639482

- Freeman-Sheldon syndrome, Autosomal dominant

  ### Freeman-Sheldon syndrome

  Freeman-Sheldon syndrome (FSS), or DA2A, is phenotypically similar to DA1. In addition to contractures of the hands and feet, FSS is characterized by oropharyngeal abnormalities, scoliosis, and a distinctive face that includes a very small oral orifice (often only a few millimeters in diameter at birth), puckered lips, and an H-shaped dimple of the chin; hence, FSS has been called 'whistling face syndrome.' The limb phenotypes of DA1 and FSS may be so similar that they can only be distinguished by the differences in facial morphology (summary by Bamshad et al., 2009). For a general phenotypic description and a discussion of genetic heterogeneity of distal arthrogryposis, see DA1 (108120).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 2
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 17:10639482

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 2
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 17:10639482

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: ATP8B1
Variant: c.208G>A
(p.Asp70Asn)
rsID: rs34719006
Ref Allele: C
Alt Allele: T
Freq: 0.2572%rare
CADD: 23.7

ClinVar Submissions (4)

- Cholestasis of pregnancy, Autosomal dominant

  ### Cholestasis of pregnancy

  Intrahepatic cholestasis of pregnancy is a reversible form of cholestasis that occurs most often in the third trimester of pregnancy and recurs in 45 to 70% of subsequent pregnancies. Symptoms include pruritus, jaundice, increased serum bile salts, and abnormal liver enzymes, all of which resolve rapidly after delivery. However, the condition is associated with fetal complications, including placental insufficiency, premature labor, fetal distress, and intrauterine death. Some women with ICP may also be susceptible to oral contraceptive-induced cholestasis (OCIC) (summary by Pasmant et al., 2012). Genetic Heterogeneity of Intrahepatic Cholestasis of Pregnancy See also ICP3 (614972), caused by mutation in the ABCB4 gene (171060).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 05, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 4
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 18:57706561
  OMIM Allelic Variant: 602397.0010

- Cholestasis, benign recurrent intrahepatic 1

  ### Cholestasis, benign recurrent intrahepatic 1

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 05, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 4
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 18:57706561
  OMIM Allelic Variant: 602397.0010

- Progressive familial intrahepatic cholestasis 2, Autosomal recessive

  ### Progressive familial intrahepatic cholestasis 2

  ATP8B1 deficiency encompasses a phenotypic spectrum ranging from severe to intermediate to mild, based on an individual's clinical findings and laboratory test results, including liver biopsy. Severe ATP8B1 deficiency is characterized by onset of symptoms of cholestasis (pruritus and attacks of jaundice) within the first few months of life. Secondary manifestations such as coagulopathy (due to vitamin K deficiency), malabsorption, and poor weight gain may present earlier than age three months. Without surgical intervention, cirrhosis and evolution to end-stage hepatic failure and death usually ensue before the third decade. Mild ATP8B1 deficiency is characterized by intermittent episodes of cholestasis manifest as severe pruritus and jaundice; chronic liver damage does not typically develop. In contrast to patients in whom bouts of cholestasis are induced only by particular triggers known to increase risk of cholestasis (drug exposure, shifts in hormonal milieu [including those resulting from ingestion of contraceptive drugs or from pregnancy], coexistent malignancy), some or all bouts of cholestasis in individuals with mild ATP8B1 deficiency have different or unknown triggers.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 05, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 4
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 18:57706561
  OMIM Allelic Variant: 602397.0010

- Progressive intrahepatic cholestasis, Autosomal recessive

  ### Progressive intrahepatic cholestasis

  ATP8B1 deficiency encompasses a phenotypic spectrum ranging from severe to intermediate to mild, based on an individual's clinical findings and laboratory test results, including liver biopsy. Severe ATP8B1 deficiency is characterized by onset of symptoms of cholestasis (pruritus and attacks of jaundice) within the first few months of life. Secondary manifestations such as coagulopathy (due to vitamin K deficiency), malabsorption, and poor weight gain may present earlier than age three months. Without surgical intervention, cirrhosis and evolution to end-stage hepatic failure and death usually ensue before the third decade. Mild ATP8B1 deficiency is characterized by intermittent episodes of cholestasis manifest as severe pruritus and jaundice; chronic liver damage does not typically develop. In contrast to patients in whom bouts of cholestasis are induced only by particular triggers known to increase risk of cholestasis (drug exposure, shifts in hormonal milieu [including those resulting from ingestion of contraceptive drugs or from pregnancy], coexistent malignancy), some or all bouts of cholestasis in individuals with mild ATP8B1 deficiency have different or unknown triggers.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 05, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 4
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 18:57706561
  OMIM Allelic Variant: 602397.0010

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 05, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 4
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 18:57706561
  OMIM Allelic Variant: 602397.0010

Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (2)

Hetero

CT

Gene: CTRC
Variant: c.640-42G>C
rsID: rs199897030
Ref Allele: G
Alt Allele: C
Freq: 0.2636%rare
CADD: 0.224

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 25, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:15445555

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GC

Gene: PNKD
Variant: c.353-26C>T
rsID: rs201632828
Ref Allele: C
Alt Allele: T
Freq: 0.2668%rare
CADD: 0.037

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:218340003

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: ABCA4
Variant: c.5882G>A
(p.Gly1961Glu)
rsID: rs1800553
Ref Allele: C
Alt Allele: T
Freq: 0.2692%rare
CADD: 26.5

ClinVar Submissions (17)

- ABCA4-Related Disorders

  ### ABCA4-Related Disorders

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 04, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 17
  Clinical Significance: Pathogenic/Likely pathogenic, risk factor
  Assembly: GRCh38
  Chromosome/Position: 1:94008251
  OMIM Allelic Variant: 601691.0007

- Age-related macular degeneration 2, Autosomal dominant

  ### Age-related macular degeneration 2

  Age-related macular degeneration is an eye disease that is a leading cause of vision loss in older people in developed countries. The vision loss usually becomes noticeable in a person's sixties or seventies and tends to worsen over time.Age-related macular degeneration mainly affects central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces. The vision loss in this condition results from a gradual deterioration of light-sensing cells in the tissue at the back of the eye that detects light and color (the retina). Specifically, age-related macular degeneration affects a small area near the center of the retina, called the macula, which is responsible for central vision. Side (peripheral) vision and night vision are generally not affected, but reduced dim light (scotopic) vision often occurs in the early stages of the disease.Researchers have described two major types of age-related macular degeneration, known as the dry form and the wet form. The dry form is much more common, accounting for 85 to 90 percent of all cases of age-related macular degeneration. It is characterized by a buildup of yellowish deposits called drusen beneath the retina and vision loss that worsens slowly over time. The condition typically affects vision in both eyes, although vision loss often occurs in one eye before the other.The wet form of age-related macular degeneration is associated with severe vision loss that can worsen rapidly. This form of the condition is characterized by the growth of abnormal, fragile blood vessels underneath the macula. These vessels leak blood and fluid, which damages the macula and makes central vision appear blurry and distorted.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 04, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 17
  Clinical Significance: Pathogenic/Likely pathogenic, risk factor
  Assembly: GRCh38
  Chromosome/Position: 1:94008251
  OMIM Allelic Variant: 601691.0007

- Cone-rod dystrophy 3

  ### Cone-rod dystrophy 3

  Cone-rod dystrophy is a group of related eye disorders that causes vision loss, which becomes more severe over time. These disorders affect the retina, which is the layer of light-sensitive tissue at the back of the eye. In people with cone-rod dystrophy, vision loss occurs as the light-sensing cells of the retina gradually deteriorate.The first signs and symptoms of cone-rod dystrophy, which often occur in childhood, are usually decreased sharpness of vision (visual acuity) and increased sensitivity to light (photophobia). These features are typically followed by impaired color vision (dyschromatopsia), blind spots (scotomas) in the center of the visual field, and partial side (peripheral) vision loss. Over time, affected individuals develop night blindness and a worsening of their peripheral vision, which can limit independent mobility. Decreasing visual acuity makes reading increasingly difficult and most affected individuals are legally blind by mid-adulthood. As the condition progresses, individuals may develop involuntary eye movements (nystagmus).There are more than 30 types of cone-rod dystrophy, which are distinguished by their genetic cause and their pattern of inheritance: autosomal recessive, autosomal dominant, and X-linked. Additionally, cone-rod dystrophy can occur alone without any other signs and symptoms or it can occur as part of a syndrome that affects multiple parts of the body.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 04, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 17
  Clinical Significance: Pathogenic/Likely pathogenic, risk factor
  Assembly: GRCh38
  Chromosome/Position: 1:94008251
  OMIM Allelic Variant: 601691.0007

- Inborn genetic diseases

  ### Inborn genetic diseases

  Diseases that are caused by genetic mutations present during embryo or fetal development, although they may be observed later in life. The mutations may be inherited from a parent's genome or they may be acquired in utero.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 04, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 17
  Clinical Significance: Pathogenic/Likely pathogenic, risk factor
  Assembly: GRCh38
  Chromosome/Position: 1:94008251
  OMIM Allelic Variant: 601691.0007

- MACULAR DEGENERATION, AGE-RELATED, 2, SUSCEPTIBILITY TO

  ### MACULAR DEGENERATION, AGE-RELATED, 2, SUSCEPTIBILITY TO

  Macular dystrophy is a nonspecific term for premature retinal cell aging and cell death, generally confied to the macula in which no clear extrinsic cause is evident.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 04, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 17
  Clinical Significance: Pathogenic/Likely pathogenic, risk factor
  Assembly: GRCh38
  Chromosome/Position: 1:94008251
  OMIM Allelic Variant: 601691.0007

- Macular dystrophy

  ### Macular dystrophy

  A group of disorders involving predominantly the posterior portion of the ocular fundus, due to degeneration in the sensory layer of the RETINA; RETINAL PIGMENT EPITHELIUM; BRUCH MEMBRANE; CHOROID; or a combination of these tissues.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 04, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 17
  Clinical Significance: Pathogenic/Likely pathogenic, risk factor
  Assembly: GRCh38
  Chromosome/Position: 1:94008251
  OMIM Allelic Variant: 601691.0007

- Retinal dystrophy

  ### Retinal dystrophy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 04, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 17
  Clinical Significance: Pathogenic/Likely pathogenic, risk factor
  Assembly: GRCh38
  Chromosome/Position: 1:94008251
  OMIM Allelic Variant: 601691.0007

- Stargardt disease 1, Autosomal recessive

  ### Stargardt disease 1

  Stargardt macular degeneration is a genetic eye disorder that causes progressive vision loss. This disorder affects the retina, the specialized light-sensitive tissue that lines the back of the eye. Specifically, Stargardt macular degeneration affects a small area near the center of the retina called the macula. The macula is responsible for sharp central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces. In most people with Stargardt macular degeneration, a fatty yellow pigment (lipofuscin) builds up in cells underlying the macula. Over time, the abnormal accumulation of this substance can damage cells that are critical for clear central vision. In addition to central vision loss, people with Stargardt macular degeneration have problems with night vision that can make it difficult to navigate in low light. Some affected individuals also have impaired color vision. The signs and symptoms of Stargardt macular degeneration typically appear in late childhood to early adulthood and worsen over time.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 04, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 17
  Clinical Significance: Pathogenic/Likely pathogenic, risk factor
  Assembly: GRCh38
  Chromosome/Position: 1:94008251
  OMIM Allelic Variant: 601691.0007

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 04, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 17
  Clinical Significance: Pathogenic/Likely pathogenic, risk factor
  Assembly: GRCh38
  Chromosome/Position: 1:94008251
  OMIM Allelic Variant: 601691.0007

High clinical importance, Likely pathogenic — This rare variant causes Stargardt Disease in a recessive manner. It was hypothesized to increase susceptibility to age-related macular degeneration, but subsequent studies have contradicted this hypothesis.

Clinically Significant Pathogenic/Likely pathogenic, risk factor

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (38)

Hetero

CT

Gene: TAP1
Variant: c.1231-3C>T
rsID: rs56366814
Ref Allele: G
Alt Allele: A
Freq: 0.2763%rare
CADD: 9.337

ClinVar Submissions (1)

- Bare lymphocyte syndrome type 1, Autosomal recessive

  ### Bare lymphocyte syndrome type 1

  Bare lymphocyte syndrome type I (BLS I) is an inherited disorder of the immune system (primary immunodeficiency). Immunodeficiencies are conditions in which the immune system is not able to protect the body effectively from foreign invaders such as bacteria or viruses. Starting in childhood, most people with BLS I develop recurrent bacterial infections in the lungs and airways (respiratory tract). These recurrent infections can lead to a condition called bronchiectasis, which damages the passages leading from the windpipe to the lungs (bronchi) and can cause breathing problems.Many people with BLS I also have open sores (ulcers) on their skin, usually on the face, arms, and legs. These ulcers typically develop in adolescence or young adulthood. Some people with BLS I have no symptoms of the condition.People with BLS I have a shortage of specialized immune proteins called major histocompatibility complex (MHC) class I proteins on cells, including infection-fighting white blood cells (lymphocytes), which is where the condition got its name.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 06, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 6:32850520

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GA

Gene: CSF3R
Variant: c.1213G>A
(p.Glu405Lys)
rsID: rs3918019
Ref Allele: C
Alt Allele: T
Freq: 0.2803%rare
CADD: 17.71

ClinVar Submissions (1)

- Neutropenia, severe congenital, 7, autosomal recessive, Autosomal recessive

  ### Neutropenia, severe congenital, 7, autosomal recessive

  Severe congenital neutropenia-7 is an autosomal recessive immunodeficiency characterized by onset of recurrent infections in infancy or early childhood. Patients have peripheral neutropenia, although bone marrow biopsy shows normal granulocyte maturation. The neutropenia is not responsive to treatment with G-CSF, but may be responsive to GM-CSF (summary by Triot et al., 2014 and Klimiankou et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of severe congenital neutropenia, see SCN1 (202700).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 21, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 1:36471505

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: CPA6
Variant: c.799G>A
(p.Gly267Arg)
rsID: rs61738009
Ref Allele: C
Alt Allele: T
Freq: 0.2811%rare
CADD: 27.1

ClinVar Submissions (6)

- Epilepsy, familial temporal lobe, 5, Autosomal dominant

  ### Epilepsy, familial temporal lobe, 5

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 25, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 6
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 8:67483807
  OMIM Allelic Variant: 609562.0002

- Febrile seizures, familial, 11, Autosomal recessive

  ### Febrile seizures, familial, 11

  Familial febrile seizures-11 is an autosomal recessive seizure disorder characterized by early childhood onset of simple or complex seizures associated with fever. These seizures usually remit later in childhood with no neurologic sequelae (summary by Salzmann et al., 2012). For a general description and a discussion of genetic heterogeneity of familial febrile seizures, see FEB1 (121210).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 25, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 6
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 8:67483807
  OMIM Allelic Variant: 609562.0002

- Global developmental delay

  ### Global developmental delay

  A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age. [DDD:hvfirth, HPO:sdoelken]

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 25, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 6
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 8:67483807
  OMIM Allelic Variant: 609562.0002

- Rolandic epilepsy

  ### Rolandic epilepsy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 25, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 6
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 8:67483807
  OMIM Allelic Variant: 609562.0002

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 25, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 6
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 8:67483807
  OMIM Allelic Variant: 609562.0002

Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (3)

Hetero

CT

Gene: RFXANK
Variant: c.337+4C>T
rsID: rs187331767
Ref Allele: C
Alt Allele: T
Freq: 0.2883%rare
CADD: 9.089

ClinVar Submissions (2)

- Bare lymphocyte syndrome 2, Autosomal dominant

  ### Bare lymphocyte syndrome 2

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 04, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 19:19197255

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 04, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 19:19197255

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CT

Gene: OTOG
Variant: c.879G>A
(p.Lys293=)
rsID: rs570688276
Ref Allele: G
Alt Allele: A
Freq: 0.2891%rare
CADD: 8.72

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 18, 2015
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 11:17557301

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: SPINK5
Variant: c.2243A>G
(p.Glu748Gly)
rsID: rs181639116
Ref Allele: A
Alt Allele: G
Freq: 0.2939%rare
CADD: 22.4

ClinVar Submissions (5)

- Netherton syndrome, Autosomal recessive

  ### Netherton syndrome

  Netherton syndrome is a rare and severe autosomal recessive skin disorder characterized by congenital erythroderma, a specific hair-shaft abnormality, and atopic manifestations with high IgE levels. Generalized scaly erythroderma is apparent at or soon after birth and usually persists. Scalp hair is sparse and brittle with a characteristic 'bamboo' shape under light microscopic examination due to invagination of the distal part of the hair shaft to its proximal part. Atopic manifestations include eczema-like rashes, atopic dermatitis, pruritus, hay fever, angioedema, urticaria, high levels of IgE in the serum, and hypereosinophilia. Life-threatening complications are frequent during the neonatal period, including hypernatremic dehydration, hypothermia, extreme weight loss, bronchopneumonia, and sepsis. During childhood, failure to thrive is common as a result of malnutrition, metabolic disorders, chronic erythroderma, persistent cutaneous infections, or enteropathy (summary by Bitoun et al., 2002).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 29, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 5
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 5:148118988

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 29, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 5
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 5:148118988

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

AG

Gene: ERLIN2
Variant: c.696G>A
(p.Lys232=)
rsID: rs138164407
Ref Allele: G
Alt Allele: A
Freq: 0.3098%rare
CADD: 20.4

ClinVar Submissions (3)

- Spastic paraplegia

  ### Spastic paraplegia

  Spasticity and weakness of the leg and hip muscles.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 11, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 8:37751672

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 11, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 8:37751672

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: TG
Variant: c.144C>T
(p.Tyr48=)
rsID: rs114436500
Ref Allele: C
Alt Allele: T
Freq: 0.3178%rare
CADD: 2.413

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 07, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 8:132868191

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: C15orf41
Variant: c.427-15C>G
rsID: rs139444685
Ref Allele: C
Alt Allele: G
Freq: 0.3313%rare
CADD: 13.71

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 15:36692111

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

CG

Gene: POLR3A
Variant: c.927C>T
(p.Asp309=)
rsID: rs41274610
Ref Allele: G
Alt Allele: A
Freq: 0.3385%rare
CADD: 11.37

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 27, 2014
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 10:78021981

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: CACNA1D
Variant: c.3952C>T
(p.Pro1318Ser)
rsID: rs72556360
Ref Allele: C
Alt Allele: T
Freq: 0.3432%rare
CADD: 18.35

ClinVar Submissions (2)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 27, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 3:53769994

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: PTRH2
Variant: c.61G>A
(p.Val21Ile)
rsID: rs76310651
Ref Allele: C
Alt Allele: T
Freq: 0.3472%rare
CADD: 17.55

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 29, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 17:59697918

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CT

Gene: DHCR24
Variant: c.*2442G>T
rsID: rs115017311
Ref Allele: C
Alt Allele: A
Freq: 0.3584%rare
CADD: 11.16

ClinVar Submissions (1)

- Desmosterolosis, Autosomal recessive

  ### Desmosterolosis

  Desmosterolosis is a rare autosomal recessive disorder characterized by multiple congenital anomalies and elevated levels of the cholesterol precursor desmosterol in plasma, tissue, and cultured cells (summary by Waterham et al., 2001).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 1:54849791

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CA

Gene: PTPN11
Variant: c.*325G>A
rsID: rs192080780
Ref Allele: G
Alt Allele: A
Freq: 0.3687%rare
CADD: 15.28

ClinVar Submissions (1)

- Metachondromatosis, Autosomal dominant

  ### Metachondromatosis

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 12:112506117

- Noonan syndrome

  ### Noonan syndrome

  Noonan syndrome (NS) is characterized by characteristic facies, short stature, congenital heart defect, and developmental delay of variable degree. Other findings can include broad or webbed neck, unusual chest shape with superior pectus carinatum and inferior pectus excavatum, cryptorchidism, varied coagulation defects, lymphatic dysplasias, and ocular abnormalities. Although birth length is usually normal, final adult height approaches the lower limit of normal. Congenital heart disease occurs in 50%-80% of individuals. Pulmonary valve stenosis, often with dysplasia, is the most common heart defect and is found in 20%-50% of individuals. Hypertrophic cardiomyopathy, found in 20%-30% of individuals, may be present at birth or develop in infancy or childhood. Other structural defects include atrial and ventricular septal defects, branch pulmonary artery stenosis, and tetralogy of Fallot. Up to one fourth of affected individuals have mild intellectual disability, and language impairments in general are more common in NS than in the general population.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 12:112506117

- Noonan syndrome with multiple lentigines

  ### Noonan syndrome with multiple lentigines

  Noonan syndrome with multiple lentigines (NSML) is a condition in which the cardinal features consist of lentigines, hypertrophic cardiomyopathy, short stature, pectus deformity, and dysmorphic facial features, including widely spaced eyes and ptosis. Multiple lentigines present as dispersed flat, black-brown macules, mostly on the face, neck and upper part of the trunk with sparing of the mucosa. In general, lentigines do not appear until age four to five years but then increase to the thousands by puberty. Some individuals with NSML do not exhibit lentigines. Approximately 85% of affected individuals have heart defects, including hypertrophic cardiomyopathy (HCM) (typically appearing during infancy and sometimes progressive) and pulmonary valve stenosis. Postnatal growth retardation resulting in short stature occurs in fewer than 50% of affected persons, although most affected individuals have a height that is less than the 25th percentile for age. Sensorineural hearing deficits, present in approximately 20%, are poorly characterized. Intellectual disability, typically mild, is observed in approximately 30% of persons with NSML.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 12:112506117

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GA

Gene: FOXE3
Variant: c.587G>C
(p.Gly196Ala)
rsID: rs281865461
Ref Allele: G
Alt Allele: C
Freq: 0.3743%rare
CADD: 8.543

ClinVar Submissions (2)

- Anterior segment mesenchymal dysgenesis, Autosomal dominant

  ### Anterior segment mesenchymal dysgenesis

  Anterior segment dysgeneses (ASGD or ASMD) are a heterogeneous group of developmental disorders affecting the anterior segment of the eye, including the cornea, iris, lens, trabecular meshwork, and Schlemm canal. The clinical features of ASGD include iris hypoplasia, an enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, an abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface (summary by Cheong et al., 2016). Anterior segment dysgenesis is sometimes divided into subtypes including aniridia (see 106210), Axenfeld and Rieger anomalies, iridogoniodysgenesis, Peters anomaly, and posterior embryotoxon (Gould and John, 2002). Some patients with ASGD1 have been reported with the Peters anomaly subtype. In its simplist form, Peters anomaly involves a central corneal opacity, but it may also involve adherent iris strands. Some patients have keratolenticular content or cataract. The underlying defects in this form of congenital corneal opacity reside in the posterior stroma, Descemet membrane, and corneal endothelium. The disorder results from abnormal migration or function of neural crest cells and may include abnormalities of other anterior segment structures, such as the lens and iris (summary by Withers et al., 1999).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 02, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:47416902

- Congenital primary aphakia, Autosomal recessive

  ### Congenital primary aphakia

  Anterior segment dysgeneses are a heterogeneous group of developmental disorders affecting the anterior segment of the eye, including the cornea, iris, lens, trabecular meshwork, and Schlemm canal. The clinical features of ASGD include iris hypoplasia, an enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, an abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface (summary by Cheong et al., 2016). Anterior segment dysgenesis is sometimes divided into subtypes, including aniridia (see 106210), Axenfeld and Rieger anomalies, iridogoniodysgenesis, Peters anomaly, and posterior embryotoxon (Gould and John, 2002). Some patients with ASGD2 have been reported with a congenital primary aphakia subtype. Congenital primary aphakia is a rare developmental disorder characterized by absence of the lens, the development of which is normally induced during the fourth to fifth week of human embryogenesis. This original failure leads, in turn, to complete aplasia of the anterior segment of the eye, which is the diagnostic histologic criterion for CPAK. In contrast, in secondary aphakia, lens induction occurs and the lens vesicle develops to some degree, but is progressively resorbed perinatally, resulting in less severe ocular defects (summary by Valleix et al., 2006).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 02, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:47416902

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 02, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:47416902

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

GC

Gene: ACADVL
Variant: c.308A>G
(p.Lys103Arg)
rsID: rs140566084
Ref Allele: A
Alt Allele: G
Freq: 0.3743%rare
CADD: 18.61

ClinVar Submissions (2)

- Very long chain acyl-CoA dehydrogenase deficiency, Autosomal recessive

  ### Very long chain acyl-CoA dehydrogenase deficiency

  Deficiency of very long-chain acyl-CoA dehydrogenase (VLCAD), which catalyzes the initial step of mitochondrial ß-oxidation of long-chain fatty acids with a chain length of 14 to 20 carbons, is associated with three phenotypes. The severe early-onset cardiac and multiorgan failure form typically presents in the first months of life with hypertrophic or dilated cardiomyopathy, pericardial effusion, and arrhythmias, as well as hypotonia, hepatomegaly, and intermittent hypoglycemia. The hepatic or hypoketotic hypoglycemic form typically presents during early childhood with hypoketotic hypoglycemia and hepatomegaly, but without cardiomyopathy. The later-onset episodic myopathic form presents with intermittent rhabdomyolysis provoked by exercise, muscle cramps and/or pain, and/or exercise intolerance. Hypoglycemia typically is not present at the time of symptoms.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 15, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 17:7220796

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 15, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 17:7220796

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

AG

Gene: USH1G
Variant: c.-173G>C
rsID: rs570755897
Ref Allele: C
Alt Allele: G
Freq: 0.3902%rare
CADD: 3.253

ClinVar Submissions (1)

- Retinitis pigmentosa-deafness syndrome

  ### Retinitis pigmentosa-deafness syndrome

  Usher syndrome is a condition characterized by partial or total hearing loss and vision loss that worsens over time. The hearing loss is classified as sensorineural, which means that it is caused by abnormalities of the inner ear. The loss of vision is caused by an eye disease called retinitis pigmentosa (RP), which affects the layer of light-sensitive tissue at the back of the eye (the retina). Vision loss occurs as the light-sensing cells of the retina gradually deteriorate. Night vision loss begins first, followed by blind spots that develop in the side (peripheral) vision. Over time, these blind spots enlarge and merge to produce tunnel vision. In some cases, vision is further impaired by clouding of the lens of the eye (cataracts). However, many people with retinitis pigmentosa retain some central vision throughout their lives.Researchers have identified three major types of Usher syndrome, designated as types I, II, and III. These types are distinguished by the severity of hearing loss, the presence or absence of balance problems, and the age at which signs and symptoms appear. The types are further divided into subtypes based on their genetic cause.Most individuals with Usher syndrome type I are born with severe to profound hearing loss. Progressive vision loss caused by retinitis pigmentosa becomes apparent in childhood. This type of Usher syndrome also causes abnormalities of the vestibular system, which is the part of the inner ear that helps maintain the body's balance and orientation in space. As a result of the vestibular abnormalities, children with the condition have trouble with balance. They begin sitting independently and walking later than usual, and they may have difficulty riding a bicycle and playing certain sports.Usher syndrome type II is characterized by hearing loss from birth and progressive vision loss that begins in adolescence or adulthood. The hearing loss associated with this form of Usher syndrome ranges from mild to severe and mainly affects the ability to hear high-frequency sounds. For example, it is difficult for affected individuals to hear high, soft speech sounds, such as those of the letters d and t. The degree of hearing loss varies within and among families with this condition, and it may become more severe over time. Unlike the other forms of Usher syndrome, type II is not associated with vestibular abnormalities that cause difficulties with balance.People with Usher syndrome type III experience hearing loss and vision loss beginning somewhat later in life. Unlike the other forms of Usher syndrome, type III is usually associated with normal hearing at birth. Hearing loss typically begins during late childhood or adolescence, after the development of speech, and becomes more severe over time. By middle age, most affected individuals have profound hearing loss. Vision loss caused by retinitis pigmentosa also develops in late childhood or adolescence. Some people with Usher syndrome type III develop vestibular abnormalities that cause problems with balance.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 17:74923246

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CG

Gene: GFI1
Variant: c.-54G>T
rsID: rs139390290
Ref Allele: C
Alt Allele: A
Freq: 0.3934%rare
CADD: 8.828

ClinVar Submissions (1)

- Severe congenital neutropenia

  ### Severe congenital neutropenia

  Severe congenital neutropenia is a condition that causes affected individuals to be prone to recurrent infections. People with this condition have a shortage (deficiency) of neutrophils, a type of white blood cell that plays a role in inflammation and in fighting infection. The deficiency of neutrophils, called neutropenia, is apparent at birth or soon afterward. It leads to recurrent infections beginning in infancy, including infections of the sinuses, lungs, and liver. Affected individuals can also develop fevers and inflammation of the gums (gingivitis) and skin. Approximately 40 percent of affected people have decreased bone density (osteopenia) and may develop osteoporosis, a condition that makes bones progressively more brittle and prone to fracture. In people with severe congenital neutropenia, these bone disorders can begin at any time from infancy through adulthood.Approximately 20 percent of people with severe congenital neutropenia develop certain cancerous conditions of the blood, particularly myelodysplastic syndrome or leukemia during adolescence.Some people with severe congenital neutropenia have additional health problems such as seizures, developmental delay, or heart and genital abnormalities.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:92483541

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CA

Gene: BTD
Variant: c.*211G>A
rsID: rs78601074
Ref Allele: G
Alt Allele: A
Freq: 0.4117%rare
CADD: 0.557

ClinVar Submissions (1)

- Biotinidase deficiency, Autosomal recessive

  ### Biotinidase deficiency

  If untreated, young children with profound biotinidase deficiency usually exhibit neurologic abnormalities including seizures, hypotonia, ataxia, developmental delay, vision problems, hearing loss, and cutaneous abnormalities (e.g., alopecia, skin rash, candidiasis). Older children and adolescents with profound biotinidase deficiency often exhibit motor limb weakness, spastic paresis, and decreased visual acuity. Once vision problems, hearing loss, and developmental delay occur, they are usually irreversible, even with biotin therapy. Individuals with partial biotinidase deficiency may have hypotonia, skin rash, and hair loss, particularly during times of stress.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 3:15645699

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GA

Gene: EOGT
Variant: c.783C>T
(p.His261=)
rsID: rs147327086
Ref Allele: G
Alt Allele: A
Freq: 0.4133%rare
CADD: 14.8

ClinVar Submissions (1)

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 08, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 3:68998059

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: NSUN2
Variant: c.510G>A
(p.Leu170=)
rsID: rs144888290
Ref Allele: C
Alt Allele: T
Freq: 0.4253%rare
CADD: 2.424

ClinVar Submissions (2)

- History of neurodevelopmental disorder

  ### History of neurodevelopmental disorder

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:6623241

- Intellectual Disability, Recessive

  ### Intellectual Disability, Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:6623241

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CT

Gene: CLPB
Variant: c.668G>A
(p.Ser223Asn)
rsID: rs143097446
Ref Allele: C
Alt Allele: T
Freq: 0.4292%rare
CADD: 16.58

ClinVar Submissions (4)

- 3-methylglutaconic aciduria with cataracts, neurologic involvement, and neutropenia, Autosomal recessive

  ### 3-methylglutaconic aciduria with cataracts, neurologic involvement, and neutropenia

  CLPB (caseinolytic peptidase B) deficiency is characterized by neurologic involvement and neutropenia, which range from severe to mild. To date, a total of 26 individuals from 16 families have been reported. In severe CLPB deficiency, death usually occurs at a few months of age as a result of significant neonatal neurologic involvement (hyperekplexia or absence of voluntary movements, hypotonia or hypertonia, swallowing problems, respiratory insufficiency, and epilepsy) and severe neutropenia associated with life-threatening infections. In moderate CLPB deficiency neurologic abnormalities in infancy are comparable to but less severe than those observed in the severe phenotype (e.g., hypotonia and feeding problems) and in later childhood can include spasticity, a progressive movement disorder (ataxia, dystonia, and/or dyskinesia), epilepsy, and intellectual disability ranging from mild learning disability to limited development of all cognitive and motor functions. Neutropenia is variable, but not life threatening. In mild CLPB deficiency there is no neurologic involvement, intellect is normal, and neutropenia is mild and intermittent. Life expectancy is normal.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 04, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:72372993

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 04, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:72372993

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 04, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:72372993

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: ATP2A1
Variant: c.663C>G
(p.Gly221=)
rsID: rs113803159
Ref Allele: C
Alt Allele: G
Freq: 0.434%rare
CADD: 5.684

ClinVar Submissions (3)

- Brody myopathy, Autosomal dominant

  ### Brody myopathy

  Brody myopathy, a disorder of fast-twitch skeletal muscle function, is characterized by exercise-induced impairment of skeletal muscle relaxation, stiffening, and cramps, predominantly in the arms, legs, and eyelids (summary by Odermatt et al., 2000).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 30, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 16:28887457

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 30, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 16:28887457

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 30, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 16:28887457

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

CG

Gene: PXDN
Variant: c.3850G>T
(p.Val1284Leu)
rsID: rs147066927
Ref Allele: C
Alt Allele: A
Freq: 0.4492%rare
CADD: 21.8

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 2:1643470

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

CA

Gene: MYH7
Variant: c.*20G>A
rsID: rs45548631
Ref Allele: C
Alt Allele: T
Freq: 0.4547%rare
CADD: 10.53

ClinVar Submissions (2)

- Dilated Cardiomyopathy, Dominant

  ### Dilated Cardiomyopathy, Dominant

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 14:23412834

- Hypertrophic cardiomyopathy

  ### Hypertrophic cardiomyopathy

  A condition in which the myocardium is hypertrophied without an obvious cause. The hypertrophy is generally asymmetric and may be associated with obstruction of the ventricular outflow tract.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 14:23412834

- Left ventricular noncompaction cardiomyopathy

  ### Left ventricular noncompaction cardiomyopathy

  An uncommon congenital abnormality where the left ventricular myocardium fails to compact during embryonic development, leading to cardiomyopathy with a variable degree of ventricular dysfunction. There is genetic heterogeneity and phenotypic variability. Characteristically, there are typically deep trabeculations in the noncompacted area, with varying proportions of the LV myocardium compacted. LV noncompaction is associated with rhythm abnormalities including Wolff-Parkinson-White syndrome, conduction defects, and ventricular tachyarrhythmias.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 14:23412834

- Myopathy, distal, 1, Autosomal dominant

  ### Myopathy, distal, 1

  Laing distal myopathy is characterized by early-onset weakness (usually before age 5 years) that initially involves the dorsiflexors of the ankles and great toes and then the finger extensors, especially those of the third and fourth fingers. Weakness of the neck flexors is seen in most affected individuals and mild facial weakness is often present. After distal weakness has been present for more than ten years, mild proximal weakness may be observed. Life expectancy is normal.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 14:23412834

- Myosin storage myopathy, Autosomal dominant

  ### Myosin storage myopathy

  Myosin storage myopathy, also known as hyaline body myopathy, is a congenital myopathy characterized by the accumulation of ATPase and antibody positive myosin in hyaline subsarcolemmal bodies in type I muscle fibers. The clinical features are variable, with different patients displaying proximal, scapuloperoneal, or generalized weakness and progressive or nonprogressive courses (summary by Dye et al., 2006).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 14:23412834

- Scapuloperoneal myopathy

  ### Scapuloperoneal myopathy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 14:23412834

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 14:23412834

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (2)

Hetero

CT

Gene: GABRA6
Variant: c.639A>G
(p.Gln213=)
rsID: rs34826485
Ref Allele: A
Alt Allele: G
Freq: 0.4643%rare
CADD: 17.56

ClinVar Submissions (1)

- Childhood absence epilepsy

  ### Childhood absence epilepsy

  A common generalized epilepsy syndrome occurring in children, characterized by absence seizures of short duration. The cause of the syndrome is presumed to be genetic. Genes which are associated with the condition are GABRB3, GABRG2, GABRA1, CACNA1H, GABRA1, and GABRA5.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 17, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 5:161689745

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

AG

Gene: TNXB
Variant: c.2367G>A
(p.Gly789=)
rsID: rs117182156
Ref Allele: C
Alt Allele: T
Freq: 0.4786%rare
CADD: 5.155

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 6:32089371

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: CACNB4
Variant: c.*2391T>G
rsID: rs143821304
Ref Allele: A
Alt Allele: C
Freq: 0.4977%rare
CADD: 15.69

ClinVar Submissions (1)

- Episodic ataxia

  ### Episodic ataxia

  Periodic spells of incoordination and imbalance, that is, episodes of ataxia typically lasting from 10 minutes to several hours or days.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:151836728

- Juvenile myoclonic epilepsy, Autosomal dominant

  ### Juvenile myoclonic epilepsy

  Juvenile myoclonic epilepsy is a subtype of idiopathic generalized epilepsy (EIG; see 600669) affecting up to 26% of all individuals with EIG. Individuals with JME have afebrile seizures only, with onset in adolescence of myoclonic jerks. Myoclonic jerks occur usually in the morning (Janz and Durner, 1997). Genetic Heterogeneity of Juvenile Myoclonic Seizures Susceptibility to EJM can be conferred by variation in several other genes: EJM5 (611136), by variation in the GABRA1 gene (137160) on 5q34; EJM6 (see 607682), by variation in the CACNB4 gene (601949) on 2q23; EJM7 (see 613060), by variation in the GABRD gene (137163) on 1p36; EJM8 (see 607628), by variation in the CLCN2 gene (600570) on 3q27; and EJM10 (617924), by variation in the ICK gene (612325) on chromosome 6p12. In addition, EJM loci have been identified by linkage analysis: EJM2 (see 604827) on 15q14, EJM3 (608816) on 6p21, EJM4 (611364) on 5q12-q14, and EJM9 (614280) on 2q33-q36.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:151836728

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

AC

Gene: TNXB
Variant: c.7168+19C>A
rsID: rs11752495
Ref Allele: G
Alt Allele: T
Freq: 0.5009%rare
CADD: 4.538

ClinVar Submissions (2)

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 24, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 6:32062138

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 24, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 6:32062138

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

GT

Gene: TNXB
Variant: c.6811G>C
(p.Val2271Leu)
rsID: rs140770834
Ref Allele: C
Alt Allele: G
Freq: 0.5009%rare
CADD: 0.001

ClinVar Submissions (2)

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 24, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 6:32064851

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 24, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 6:32064851

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

CG

Gene: INF2
Variant: c.3108T>C
(p.Leu1036=)
rsID: rs186075307
Ref Allele: T
Alt Allele: C
Freq: 0.5113%rare
CADD: 0.211

ClinVar Submissions (4)

- Charcot-Marie-Tooth disease, dominant intermediate E, Autosomal dominant

  ### Charcot-Marie-Tooth disease, dominant intermediate E

  Autosomal dominant intermediate Charcot-Marie-Tooth disease E with focal segmental glomerulonephritis is characterized by the neurologic features of CMT, including distal muscle weakness and atrophy and distal sensory loss, and the features of FSGS, including proteinuria, progression to end-stage renal disease, and a characteristic histologic pattern on renal biopsy (summary by Boyer et al., 2011). Isolated focal segmental glomerulosclerosis-5 (FSGS5; 613237) is also caused by heterozygous mutation in the INF2 gene. For a discussion of genetic heterogeneity of CMTDI, see 606482.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 27, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 14:104714270

- Focal segmental glomerulosclerosis

  ### Focal segmental glomerulosclerosis

  A clinicopathological syndrome or diagnostic term for a type of glomerular injury that has multiple causes, primary or secondary. Clinical features include PROTEINURIA, reduced GLOMERULAR FILTRATION RATE, and EDEMA. Kidney biopsy initially indicates focal segmental glomerular consolidation (hyalinosis) or scarring which can progress to globally sclerotic glomeruli leading to eventual KIDNEY FAILURE.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 27, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 14:104714270

- Focal segmental glomerulosclerosis 5

  ### Focal segmental glomerulosclerosis 5

  Focal segmental glomerulosclerosis (FSGS) is a pathologic entity associated clinically with proteinuria, the nephrotic syndrome (NPHS), and progressive loss of renal function. It is a common cause of end-stage renal disease (ESRD) (Meyrier, 2005). Dominant intermediate Charcot-Marie-Tooth disease E and focal segmental glomerulonephritis (CMTDIE; 614455) is also caused by heterozygous mutation in the INF2 gene. For a general phenotypic description and a discussion of genetic heterogeneity of focal segmental glomerulosclerosis and nephrotic syndrome, see FSGS1 (603278).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 27, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 14:104714270

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 27, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 14:104714270

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

TC

Gene: NPHP1
Variant: c.940-17G>A
rsID: rs146343637
Ref Allele: C
Alt Allele: T
Freq: 0.5121%rare
CADD: 8.17

ClinVar Submissions (2)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 18, 2014
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:110163152

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: INF2
Variant: c.1582C>T
(p.Pro528Ser)
rsID: rs181694819
Ref Allele: C
Alt Allele: T
Freq: 0.5121%rare
CADD: 1.105

ClinVar Submissions (3)

- Focal segmental glomerulosclerosis

  ### Focal segmental glomerulosclerosis

  A clinicopathological syndrome or diagnostic term for a type of glomerular injury that has multiple causes, primary or secondary. Clinical features include PROTEINURIA, reduced GLOMERULAR FILTRATION RATE, and EDEMA. Kidney biopsy initially indicates focal segmental glomerular consolidation (hyalinosis) or scarring which can progress to globally sclerotic glomeruli leading to eventual KIDNEY FAILURE.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 30, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 14:104707849

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 30, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 14:104707849

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 30, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 14:104707849

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CT

Gene: SEPT9
Variant: c.1519+9C>T
rsID: rs148975193
Ref Allele: C
Alt Allele: T
Freq: 0.5169%rare
CADD: 0.097

ClinVar Submissions (1)

- Hereditary Neuralgic Amyotrophy (HNA)

  ### Hereditary Neuralgic Amyotrophy (HNA)

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 17:77493085

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CT

Gene: CNNM2
Variant: c.*619A>G
rsID: rs138807273
Ref Allele: A
Alt Allele: G
Freq: 0.5272%rare
CADD: 1.134

ClinVar Submissions (1)

- Renal Hypomagnesemia, Dominant

  ### Renal Hypomagnesemia, Dominant

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 10:103077799

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

AG

Gene: KARS
Variant: c.*26C>G
rsID: rs78654839
Ref Allele: G
Alt Allele: C
Freq: 0.5439%rare
CADD: 1.763

ClinVar Submissions (1)

- Charcot-Marie-Tooth, Intermediate

  ### Charcot-Marie-Tooth, Intermediate

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 16:75627869

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Homo

CC

Gene: DCHS1
Variant: c.379G>A
(p.Val127Ile)
rsID: rs112402535
Ref Allele: C
Alt Allele: T
Freq: 0.5503%rare
CADD: 22.3

ClinVar Submissions (2)

- Abnormality of the corpus callosum

  ### Abnormality of the corpus callosum

  Abnormality of the corpus callosum.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 30, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:6641235

- Abnormality of the renal pelvis

  ### Abnormality of the renal pelvis

  An abnormality of the renal pelvis.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 30, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:6641235

- Delayed speech and language development

  ### Delayed speech and language development

  A degree of language development that is significantly below the norm for a child of a specified age.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 30, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:6641235

- Generalized hypotonia

  ### Generalized hypotonia

  Generalized muscular hypotonia (abnormally low muscle tone).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 30, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:6641235

- Global developmental delay

  ### Global developmental delay

  A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age. [DDD:hvfirth, HPO:sdoelken]

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 30, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:6641235

- Hypopigmented skin patches

  ### Hypopigmented skin patches

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 30, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:6641235

- Hypoplasia of the corpus callosum

  ### Hypoplasia of the corpus callosum

  Underdevelopment of the corpus callosum.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 30, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:6641235

- Joint hypermobility

  ### Joint hypermobility

  The ability of a joint to move beyond its normal range of motion.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 30, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:6641235

- Neonatal hypotonia

  ### Neonatal hypotonia

  Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 30, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:6641235

- Periventricular gray matter heterotopia

  ### Periventricular gray matter heterotopia

  A form of gray matter heterotopia were the mislocalized gray matter is typically located periventricularly, also sometimes called subependymal heterotopia. Periventricular means beside the ventricles. This is by far the most common location for heterotopia. Subependymal heterotopia present in a wide array of variations. There can be a small single node or a large number of nodes, can exist on either or both sides of the brain at any point along the higher ventricle margins, can be small or large, single or multiple, and can form a small node or a large wavy or curved mass.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 30, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:6641235

- Relative macrocephaly

  ### Relative macrocephaly

  A relatively mild degree of macrocephaly in which the head circumference is not above two standard deviations from the mean, but appears dysproportionately large when other factors such as body stature are taken into account.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 30, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:6641235

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 30, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:6641235

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: KARS
Variant: c.*33G>A
rsID: rs111679674
Ref Allele: C
Alt Allele: T
Freq: 0.6037%rare
CADD: 1.172

ClinVar Submissions (1)

- Charcot-Marie-Tooth, Intermediate

  ### Charcot-Marie-Tooth, Intermediate

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 16:75627862

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Homo

TT

Gene: TECTA
Variant: c.5384-19G>A
rsID: rs7111480
Ref Allele: G
Alt Allele: A
Freq: 0.6244%rare
CADD: 3.172

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 11:121166559

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: SUFU
Variant: c.*3290C>G
rsID: rs112808377
Ref Allele: C
Alt Allele: G
Freq: 0.6283%rare
CADD: 13.56

ClinVar Submissions (1)

- Medulloblastoma, Autosomal dominant

  ### Medulloblastoma

  Medulloblastoma is the most common brain tumor in children. It accounts for 16% of all pediatric brain tumors, and 40% of all cerebellar tumors in childhood are medulloblastoma. Medulloblastoma occurs bimodally, with peak incidences between 3 and 4 years and 8 and 9 years of age. Approximately 10 to 15% of medulloblastomas are diagnosed in infancy. Medulloblastoma accounts for less than 1% of central nervous system (CNS) tumors in adults, with highest incidence in adults 20 to 34 years of age. In 1 to 2% of patients, medulloblastoma is associated with Gorlin syndrome (109400), a nevoid basal carcinoma syndrome. Medulloblastoma also occurs in up to 40% of patients with Turcot syndrome (276300). Medulloblastoma is thought to arise from neural stem cell precursors in the granular cell layer of the cerebellum. Standard treatment includes surgery, chemotherapy, and, depending on the age of the patient, radiation therapy (Crawford et al., 2007).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 10:102633445

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CG

Gene: MYH9
Variant: c.1108+9C>T
rsID: rs145751072
Ref Allele: G
Alt Allele: A
Freq: 0.6299%rare
CADD: 7.898

ClinVar Submissions (3)

- MYH9-related disorder

  ### MYH9-related disorder

  An autosomal dominant disorder characterized by the triad of thrombocytopenia, giant platelets, and characteristic inclusions in peripheral blood leukocytes, without other organ dysfunction; it is associated with mutation of the MYH9 gene.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 22:36319531

- Nonsyndromic Hearing Loss, Dominant

  ### Nonsyndromic Hearing Loss, Dominant

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 22:36319531

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 22:36319531

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (2)

Hetero

GA

Gene: OAT
Variant: c.-30+8C>T
rsID: rs552799531
Ref Allele: G
Alt Allele: A
Freq: 0.6379%rare
CADD: 4.344

ClinVar Submissions (1)

- Ornithine aminotransferase deficiency

  ### Ornithine aminotransferase deficiency

  Gyrate atrophy of the choroid and retina due to deficiency of ornithine aminotransferase is clinically characterized by a triad of progressive chorioretinal degeneration, early cataract formation, and type II muscle fiber atrophy. Characteristic chorioretinal atrophy with progressive constriction of the visual fields leads to blindness at the latest during the sixth decade of life. Patients generally have normal intelligence (summary by Peltola et al., 2002). See 238970 for another hyperornithinemia syndrome.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 10:124418865

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GA

Gene: IQCB1
Variant: c.1303C>T
(p.Arg435Cys)
rsID: rs11920543
Ref Allele: G
Alt Allele: A
Freq: 0.6522%rare
CADD: 25.4

ClinVar Submissions (2)

- Nephronophthisis

  ### Nephronophthisis

  The nephronophthisis (NPH) phenotype is characterized by reduced renal concentrating ability, chronic tubulointerstitial nephritis, cystic renal disease, and progression to end-stage renal disease (ESRD) before age 30 years. Three age-based clinical subtypes are recongnized: infantile, juvenile, and adolescent/adult. Infantile NPH can present in utero with oligohydramnios sequence (limb contractures, pulmonary hypoplasia and facial dysmorphisms) or postnatally with renal manifestations that progress to ESRD before age 3 years. Juvenile NPH, the most prevalent subtype, typically presents with polydipsia and polyuria, growth retardation, chronic iron-resistant anemia, or other findings related to chronic kidney disease (CKD). Hypertension is typically absent due to salt wasting. ESRD develops at a median age of 13 years. Ultrasound findings are increased echogenicity, reduced corticomedullary differentiation, and renal cysts (in 50% of affected individuals). Histologic findings include tubulointerstitial fibrosis, thickened and disrupted tubular basement membrane, sporadic corticomedullary cysts, and normal or reduced kidney size. Adolescent/ adult NPH is clinically similar to juvenile NPH, but ESRD develops at a median age of 19 years. Within a subtype inter- and intrafamilial variability in rate of progression to ESRD is considerable. Approximately 80%-90% of individuals with the NPH phenotype have no extrarenal features (i.e., they have isolated NPH); ~10%-20% have extrarenal manifestations that constitute a recognizable syndrome (e.g., Joubert syndrome, Bardet-Biedl syndrome, Jeune syndrome and related skeletal disorders, Meckel-Gruber syndrome, Senior-Løken syndrome, Leber congenital amaurosis, COACH syndrome, and oculomotor apraxia, Cogan type).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 29, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 3:121781850

- Renal dysplasia and retinal aplasia

  ### Renal dysplasia and retinal aplasia

  Senior-Loken syndrome is an autosomal recessive disease with the main features of nephronophthisis (NPHP; see 256100) and Leber congenital amaurosis (see 204000). Mutations in some of the same genes that cause nephronophthisis (see 256100) cause Senior-Loken syndrome. Genetic Heterogeneity of Senior-Loken Syndrome Other forms of SLSN include SLSN4 (606996), caused by mutation in the NPHP4 gene (607215) on chromosome 1p36; SLSN5 (609254), caused by mutation in the NPHP5 gene (IQCB1; 609237) on chromosome 3q13; SLSN6 (610189), caused by mutation in the NPHP6 gene (CEP290; 610142) on chromosome 12q21; SLSN7 (613615), caused by mutation in the SDCCAG8 gene (613524) on chromosome 1q43; SLSN8 (616307), caused by mutation in the WDR19 gene (608151) on chromosome 4p14; and SLSN9 (616629), caused by mutation in the TRAF3IP1 gene (607380) on chromosome 2q37. Another form of SLSN, SLSN3 (606995), has been mapped to a locus on chromosome 3q22, overlapping the NPHP3 locus (604387).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 29, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 3:121781850

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OpenSNP
- PubMed

Hetero

GA

Gene: PTEN
Variant: c.635-696G>C
rsID: rs34513359
Ref Allele: G
Alt Allele: C
Freq: 0.6522%rare
CADD: 3.337

ClinVar Submissions (1)

- Hereditary cancer-predisposing syndrome

  ### Hereditary cancer-predisposing syndrome

  The condition of a pattern of malignancies within a family, but not every individual's necessarily having the same neoplasm. Characteristically the tumor tends to occur at an earlier than average age, individuals may have more than one primary tumor, the tumors may be multicentric, usually more than 25 percent of the individuals in direct lineal descent from the proband are affected, and the cancer predisposition in these families behaves as an autosomal dominant trait with about 60 percent penetrance.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 01, 2015
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 10:87957157

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GC

Gene: CC2D1A
Variant: c.980C>T
(p.Ser327Leu)
rsID: rs200121704
Ref Allele: C
Alt Allele: T
Freq: 0.6538%rare
CADD: 5.053

ClinVar Submissions (3)

- History of neurodevelopmental disorder

  ### History of neurodevelopmental disorder

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 15, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 19:13918779

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 15, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 19:13918779

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 15, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 19:13918779

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: FOXC2
Variant: c.108C>T
(p.Ser36=)
rsID: rs138318843
Ref Allele: C
Alt Allele: T
Freq: 0.6761%rare
CADD: 20.4

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 16:86567443

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: SLC5A1
Variant: c.1130-9C>T
rsID: rs33914280
Ref Allele: C
Alt Allele: T
Freq: 0.6809%rare
CADD: 6.554

ClinVar Submissions (1)

- Congenital glucose-galactose malabsorption, Autosomal recessive

  ### Congenital glucose-galactose malabsorption

  Glucose/galactose malabsorption (GGM) is a rare autosomal recessive disorder caused by a defect in glucose and galactose transport across the intestinal brush border. Patients with GGM present with neonatal onset of severe life-threatening watery diarrhea and dehydration. If diagnosed and treated properly, patients can fully recover and show normal growth and development (summary by Xin and Wang, 2011).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 22:32091603

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CT

Gene: SKI
Variant: c.1311C>T
(p.Ala437=)
rsID: rs140889128
Ref Allele: C
Alt Allele: T
Freq: 0.6825%rare
CADD: 0.04

ClinVar Submissions (6)

- Cardiovascular phenotype

  ### Cardiovascular phenotype

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 29, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 1:2303939

- Shprintzen-Goldberg syndrome, Autosomal dominant

  ### Shprintzen-Goldberg syndrome

  Shprintzen-Goldberg syndrome (SGS) is characterized by: craniosynostosis of the coronal, sagittal, or lambdoid sutures; dolichocephaly; distinctive craniofacial features; skeletal changes (dolichostenomelia, arachnodactyly, camptodactyly, pes planus, pectus excavatum or carinatum, scoliosis, joint hypermobility or contractures and C1/C2 spine malformation); neurologic abnormalities; intellectual disability; and brain anomalies (hydrocephalus, dilatation of the lateral ventricles, and Chiari 1 malformation). Cardiovascular anomalies may include mitral valve prolapse, mitral regurgitation/incompetence, aortic regurgitation, and aortic root dilatation. Minimal subcutaneous fat, abdominal wall defects, myopia, and cryptorchidism in males are also characteristic findings.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 29, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 1:2303939

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 29, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 1:2303939

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 29, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 1:2303939

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (2)

Hetero

CT

Gene: BARD1
Variant: c.1569-6730T>C
rsID: rs11689134
Ref Allele: A
Alt Allele: G
Freq: 0.6865%rare
CADD: 7.689

ClinVar Submissions (1)

- Hereditary cancer-predisposing syndrome

  ### Hereditary cancer-predisposing syndrome

  The condition of a pattern of malignancies within a family, but not every individual's necessarily having the same neoplasm. Characteristically the tumor tends to occur at an earlier than average age, individuals may have more than one primary tumor, the tumors may be multicentric, usually more than 25 percent of the individuals in direct lineal descent from the proband are affected, and the cancer predisposition in these families behaves as an autosomal dominant trait with about 60 percent penetrance.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 01, 2015
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:214759285

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

AG

Gene: KCNV2
Variant: c.849G>A
(p.Glu283=)
rsID: rs17656693
Ref Allele: G
Alt Allele: A
Freq: 0.696%rare
CADD: 16.76

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 27, 2013
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 9:2718588

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: CREBBP
Variant: c.5988C>T
(p.Ala1996=)
rsID: rs181646656
Ref Allele: G
Alt Allele: A
Freq: 0.6968%rare
CADD: 7.037

ClinVar Submissions (5)

- History of neurodevelopmental disorder

  ### History of neurodevelopmental disorder

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 19, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 16:3729059

- Rubinstein-Taybi syndrome 1, Autosomal dominant

  ### Rubinstein-Taybi syndrome 1

  Rubinstein-Taybi syndrome (RSTS) is characterized by distinctive facial features, broad and often angulated thumbs and great toes, short stature, and moderate to severe intellectual disability. The characteristic craniofacial features are downslanted palpebral fissures, low-hanging columella, high palate, grimacing smile, and talon cusps. Prenatal growth is often normal; however, height, weight, and head circumference percentiles rapidly drop in the first few months of life. Obesity may occur in childhood or adolescence. IQ scores range from 25 to 79; average IQ is between 36 and 51. Other variable findings are coloboma, cataract, congenital heart defects, renal abnormalities, and cryptorchidism.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 19, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 16:3729059

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 19, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 16:3729059

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (3)

Hetero

GA

Gene: VPS13B
Variant: c.11044+33C>A
rsID: rs72676269
Ref Allele: C
Alt Allele: A
Freq: 0.6984%rare
CADD: 0.004

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 8:99859513

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

CA

Gene: PKHD1
Variant: c.7921A>G
(p.Thr2641Ala)
rsID: rs7766366
Ref Allele: T
Alt Allele: C
Freq: 0.6992%rare
CADD: 23.6

ClinVar Submissions (6)

- Autosomal recessive polycystic kidney disease, Autosomal recessive

  ### Autosomal recessive polycystic kidney disease

  Autosomal recessive polycystic kidney disease (ARPKD) belongs to a group of congenital hepatorenal fibrocystic syndromes and is a cause of significant renal and liver-related morbidity and mortality in children. The majority of individuals with ARPKD present in the neonatal period with enlarged echogenic kidneys. Renal disease is characterized by nephromegaly, hypertension, and varying degrees of renal dysfunction. More than 50% of affected individuals with ARPKD progress to end-stage renal disease (ESRD) within the first decade of life; ESRD may require kidney transplantation. Pulmonary hypoplasia resulting from oligohydramnios occurs in a number of affected infants. Approximately 30% of these infants die in the neonatal period or within the first year of life from respiratory insufficiency or superimposed pulmonary infections. With neonatal respiratory support and renal replacement therapies, the long-term survival of these infants has improved to greater than 80%. As advances in renal replacement therapy and kidney transplantation improve long-term survival, it is likely that clinical hepatobiliary disease will become a major feature of the natural history of ARPKD. In addition, a subset of individuals with this disorder are identified with hepatosplenomegaly; the renal disease is often mild and may be discovered incidentally during imaging studies of the abdomen. Approximately 50% of infants will have clinical evidence of liver involvement at diagnosis although histologic hepatic fibrosis is invariably present at birth. This can lead to progressive portal hypertension with resulting esophageal or gastric varices, enlarged hemorrhoids, splenomegaly, hypersplenism, protein-losing enteropathy, and gastrointestinal bleeding. Other hepatic findings include nonobstructed dilatation of the intrahepatic bile ducts (Caroli syndrome) and dilatation of the common bile duct, which may lead to recurrent or persistent bacterial ascending cholangitis due to dilated bile ducts and stagnant bile flow. An increasing number of affected individuals surviving the neonatal period will eventually require portosystemic shunting or liver transplantation for complications of portal hypertension or cholangitis. The classic neonatal presentation of ARPKD notwithstanding, there is significant variability in age and presenting clinical symptoms related to the relative degree of renal and biliary abnormalities.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 31, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 6:51847961

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 31, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 6:51847961

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (4)

Hetero

TC

Gene: BBS10
Variant: c.1631A>G
(p.Asn544Ser)
rsID: rs34737974
Ref Allele: T
Alt Allele: C
Freq: 0.7%rare
CADD: 3.342

ClinVar Submissions (5)

- Bardet-Biedl syndrome

  ### Bardet-Biedl syndrome

  Bardet-Biedl syndrome (BBS) is characterized by rod-cone dystrophy, truncal obesity, postaxial polydactyly, cognitive impairment, male hypogonadotropic hypogonadism, complex female genitourinary malformations, and renal abnormalities. The visual prognosis for children with BBS is poor. Night blindness is usually evident by age seven to eight years; the mean age of legal blindness is 15.5 years. Birth weight is usually normal, but significant weight gain begins within the first year and becomes a lifelong issue for most individuals. A majority of individuals have significant learning difficulties; a minority have severe impairment on IQ testing. Renal disease is a major cause of morbidity and mortality.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 24, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 12:76346354

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 24, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 12:76346354

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 24, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 12:76346354

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

TC

Gene: PDZD7
Variant: c.2144C>T
(p.Pro715Leu)
rsID: rs143414291
Ref Allele: G
Alt Allele: A
Freq: 0.712%rare
CADD: 18.76

ClinVar Submissions (2)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 25, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 10:101010745

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: BMP4
Variant: c.370+28G>A
rsID: rs72680532
Ref Allele: C
Alt Allele: T
Freq: 0.7159%rare
CADD: 13.75

ClinVar Submissions (2)

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 12, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 14:53951825

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 12, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 14:53951825

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CT

Gene: ATP7B
Variant: c.4311G>A
(p.Lys1437=)
rsID: rs73202048
Ref Allele: C
Alt Allele: T
Freq: 0.7207%rare
CADD: 12.72

ClinVar Submissions (8)

- Wilson disease, Autosomal recessive

  ### Wilson disease

  Wilson disease is a disorder of copper metabolism that can present with hepatic, neurologic, or psychiatric disturbances, or a combination of these, in individuals ranging from age three years to older than 50 years; symptoms vary among and within families. Liver disease includes recurrent jaundice, simple acute self-limited hepatitis-like illness, autoimmune-type hepatitis, fulminant hepatic failure, or chronic liver disease. Neurologic presentations include movement disorders (tremors, poor coordination, loss of fine-motor control, chorea, choreoathetosis) or rigid dystonia (mask-like facies, rigidity, gait disturbance, pseudobulbar involvement). Psychiatric disturbance includes depression, neurotic behaviors, disorganization of personality, and, occasionally, intellectual deterioration. Kayser-Fleischer rings, frequently present, result from copper deposition in Descemet's membrane of the cornea and reflect a high degree of copper storage in the body.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 03, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 8
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 13:51934843

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 03, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 8
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 13:51934843

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (4)

Hetero

CT

Gene: CD3E
Variant: c.507C>T
(p.Gly169=)
rsID: rs2231447
Ref Allele: C
Alt Allele: T
Freq: 0.7327%rare
CADD: 0.544

ClinVar Submissions (3)

- Immunodeficiency 18, Autosomal recessive

  ### Immunodeficiency 18

  Immunodeficiency-18 is an autosomal recessive primary immunodeficiency characterized by onset in infancy or early childhood of recurrent infections. The severity is variable, encompassing both a mild immunodeficiency and severe combined immunodeficiency (SCID), resulting in early death without bone marrow transplantation in some patients. Immunologic work-up of the IMD18 SCID patients shows a T cell-negative, B cell-positive, natural killer (NK) cell-positive phenotype, whereas T-cell development is not impaired in the mild form of IMD18 (summary by de Saint Basile et al., 2004).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 22, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 11:118313861

- Severe Combined Immune Deficiency

  ### Severe Combined Immune Deficiency

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 22, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 11:118313861

- Severe combined immunodeficiency disease

  ### Severe combined immunodeficiency disease

  A combined immunodeficiency primary immune deficiency that is characterized by a more severe defect in both the T- and B-lymphocyte systems.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 22, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 11:118313861

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CT

Gene: RBBP8
Variant: c.1644T>C
(p.Asp548=)
rsID: rs34780140
Ref Allele: T
Alt Allele: C
Freq: 0.7693%rare
CADD: 4.475

ClinVar Submissions (2)

- Microcephaly with mental retardation and digital anomalies, Autosomal recessive

  ### Microcephaly with mental retardation and digital anomalies

  A craniodigital syndrome marked by characteristic facies, microcephaly, retrognathia, symmetrical digital defects, and retarded mental development.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 02, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 2
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 18:22993471

- Seckel syndrome

  ### Seckel syndrome

  A rare autosomal recessive inherited syndrome caused by mutations in the ATR gene, RBBP8 gene, CENPJ gene, CEP152 gene, CEP63 gene, NIN gene, DNA2 gene, or TRAIP gene. It is characterized by intrauterine growth retardation, dwarfism, microcephaly, mental retardation, and a "bird-headed" facial appearance.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 02, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 2
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 18:22993471

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 02, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 2
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 18:22993471

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

TC

Gene: COL4A2
Variant: c.3368A>G
(p.Glu1123Gly)
rsID: rs117412802
Ref Allele: A
Alt Allele: G
Freq: 0.786%rare
CADD: 26.8

ClinVar Submissions (3)

- Hemorrhage, intracerebral, susceptibility to

  ### Hemorrhage, intracerebral, susceptibility to

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 09, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign, risk factor
  Assembly: GRCh38
  Chromosome/Position: 13:110491254
  OMIM Allelic Variant: 120090.0003

- Porencephalic cyst

  ### Porencephalic cyst

  A cavity within the cerebral hemisphere, filled with cerebrospinal fluid, that communicates directly with the ventricular system. [HPO:probinson, PMID:9279052]

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 09, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign, risk factor
  Assembly: GRCh38
  Chromosome/Position: 13:110491254
  OMIM Allelic Variant: 120090.0003

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 09, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign, risk factor
  Assembly: GRCh38
  Chromosome/Position: 13:110491254
  OMIM Allelic Variant: 120090.0003

Benign/Likely benign, risk factor

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (2)

Hetero

AG

Gene: CTNNA1
Variant: c.1062+16654T>A
rsID: rs150431826
Ref Allele: T
Alt Allele: A
Freq: 0.7884%rare
CADD: 9.003

ClinVar Submissions (1)

- Hereditary cancer-predisposing syndrome

  ### Hereditary cancer-predisposing syndrome

  The condition of a pattern of malignancies within a family, but not every individual's necessarily having the same neoplasm. Characteristically the tumor tends to occur at an earlier than average age, individuals may have more than one primary tumor, the tumors may be multicentric, usually more than 25 percent of the individuals in direct lineal descent from the proband are affected, and the cancer predisposition in these families behaves as an autosomal dominant trait with about 60 percent penetrance.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 01, 2015
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:138844372

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

TA

Gene: CTNNA1
Variant: c.1062+16658G>T
rsID: rs114249793
Ref Allele: G
Alt Allele: T
Freq: 0.7892%rare
CADD: 10.25

ClinVar Submissions (1)

- Hereditary cancer-predisposing syndrome

  ### Hereditary cancer-predisposing syndrome

  The condition of a pattern of malignancies within a family, but not every individual's necessarily having the same neoplasm. Characteristically the tumor tends to occur at an earlier than average age, individuals may have more than one primary tumor, the tumors may be multicentric, usually more than 25 percent of the individuals in direct lineal descent from the proband are affected, and the cancer predisposition in these families behaves as an autosomal dominant trait with about 60 percent penetrance.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 01, 2015
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:138844376

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GT

Gene: IFIH1
Variant: c.1641+1G>C
rsID: rs35337543
Ref Allele: C
Alt Allele: G
Freq: 0.7972%rare
CADD: 26

ClinVar Submissions (3)

- Aicardi-Goutieres syndrome 7, Autosomal dominant

  ### Aicardi-Goutieres syndrome 7

  Most characteristically, Aicardi-Goutières syndrome (AGS) manifests as an early-onset encephalopathy that usually, but not always, results in severe intellectual and physical disability. A subgroup of infants with AGS present at birth with abnormal neurologic findings, hepatosplenomegaly, elevated liver enzymes, and thrombocytopenia, a picture highly suggestive of congenital infection. Otherwise, most affected infants present at variable times after the first few weeks of life, frequently after a period of apparently normal development. Typically, they demonstrate the subacute onset of a severe encephalopathy characterized by extreme irritability, intermittent sterile pyrexias, loss of skills, and slowing of head growth. Over time, as many as 40% develop chilblain skin lesions on the fingers, toes, and ears. It is becoming apparent that atypical, sometimes milder, cases of AGS exist, and thus the true extent of the phenotype associated with pathogenic variants in the AGS-related genes is not yet known.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 03, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 2:162279995

- Singleton-Merten syndrome 1, Autosomal dominant

  ### Singleton-Merten syndrome 1

  Singleton-Merten syndrome (SGMRT) is an uncommon autosomal dominant disorder characterized by abnormalities of blood vessels, teeth, and bone. Calcifications of the aorta and aortic and mitral valves occur in childhood or puberty and can lead to early death. Dental findings include delayed primary tooth exfoliation and permanent tooth eruption, truncated tooth root formation, early-onset periodontal disease, and severe root and alveolar bone resorption associated with dysregulated mineralization, leading to tooth loss. Osseous features consist of osteoporosis, either generalized or limited to distal extremities, distal limb osteolysis, widened medullary cavities, and easy tearing of tendons from bone. Less common features are mild facial dysmorphism (high anterior hair line, broad forehead, smooth philtrum, thin upper vermilion border), generalized muscle weakness, psoriasis, early-onset glaucoma, and recurrent infections. The disorder manifests with variable inter- and intrafamilial phenotypes (summary by Rutsch et al., 2015). Genetic Heterogeneity of Singleton-Merten Syndrome An atypical form of Singleton-Merten syndrome (SGMRT2; 616298) is caused by mutation in the DDX58 gene (609631) on chromosome 9p21.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 03, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 2:162279995

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 03, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 2:162279995

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 03, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 2:162279995

Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (11)

Hetero

CG

Gene: HEXB
Variant: c.214C>T
(p.Leu72Phe)
rsID: rs147155126
Ref Allele: C
Alt Allele: T
Freq: 0.8012%rare
CADD: 18.5

ClinVar Submissions (5)

- Sandhoff disease, Autosomal recessive

  ### Sandhoff disease

  Sandhoff disease is a progressive neurodegenerative disorder characterized by an accumulation of GM2 gangliosides, particularly in neurons, and is clinically indistinguishable from Tay-Sachs disease (272800).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 26, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:74685474

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 26, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:74685474

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 26, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:74685474

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: CREBBP
Variant: c.1651C>A
(p.Leu551Ile)
rsID: rs61753381
Ref Allele: G
Alt Allele: T
Freq: 0.8028%rare
CADD: 22.4

ClinVar Submissions (8)

- History of neurodevelopmental disorder

  ### History of neurodevelopmental disorder

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 30, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 8
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 16:3781229

- Rubinstein-Taybi syndrome 1, Autosomal dominant

  ### Rubinstein-Taybi syndrome 1

  Rubinstein-Taybi syndrome (RSTS) is characterized by distinctive facial features, broad and often angulated thumbs and great toes, short stature, and moderate to severe intellectual disability. The characteristic craniofacial features are downslanted palpebral fissures, low-hanging columella, high palate, grimacing smile, and talon cusps. Prenatal growth is often normal; however, height, weight, and head circumference percentiles rapidly drop in the first few months of life. Obesity may occur in childhood or adolescence. IQ scores range from 25 to 79; average IQ is between 36 and 51. Other variable findings are coloboma, cataract, congenital heart defects, renal abnormalities, and cryptorchidism.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 30, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 8
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 16:3781229

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 30, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 8
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 16:3781229

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 30, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 8
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 16:3781229

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (4)

Hetero

GT

Gene: DICER1
Variant: c.1935G>A
(p.Pro645=)
rsID: rs61751177
Ref Allele: C
Alt Allele: T
Freq: 0.8075%rare
CADD: 4.008

ClinVar Submissions (5)

- DICER1-related pleuropulmonary blastoma cancer predisposition syndrome

  ### DICER1-related pleuropulmonary blastoma cancer predisposition syndrome

  DICER1-related disorders are a familial tumor susceptibility syndrome that confers increased risk most commonly for pleuropulmonary blastoma (PPB); ovarian sex cord-stromal tumors (Sertoli-Leydig cell tumor, juvenile granulosa cell tumor, and gynandroblastoma); cystic nephroma; and thyroid gland neoplasia (multinodular goiter, adenomas, or differentiated thyroid cancer). Less commonly observed tumors are ciliary body medulloepithelioma; botryoid-type embryonal rhabdomyosarcoma of the cervix or other sites; nasal chondromesenchymal hamartoma; renal sarcoma; pituitary blastoma; and pineoblastoma. Novel phenotypes continue to be discovered. The majority of tumors in families with a DICER1 germline pathogenic variant occur in individuals younger than age 40 years. PPB, a neoplasm that arises during lung development or shortly after birth, typically presents in infants and children younger than age six years. Age of onset of ovarian sex cord-stromal tumors is not well defined. CN presents in children younger than age four years.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 11, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 14:95113197

- Hereditary cancer-predisposing syndrome

  ### Hereditary cancer-predisposing syndrome

  The condition of a pattern of malignancies within a family, but not every individual's necessarily having the same neoplasm. Characteristically the tumor tends to occur at an earlier than average age, individuals may have more than one primary tumor, the tumors may be multicentric, usually more than 25 percent of the individuals in direct lineal descent from the proband are affected, and the cancer predisposition in these families behaves as an autosomal dominant trait with about 60 percent penetrance.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 11, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 14:95113197

- Pleuropulmonary blastoma, Autosomal dominant

  ### Pleuropulmonary blastoma

  DICER1-related disorders are a familial tumor susceptibility syndrome that confers increased risk most commonly for pleuropulmonary blastoma (PPB); ovarian sex cord-stromal tumors (Sertoli-Leydig cell tumor, juvenile granulosa cell tumor, and gynandroblastoma); cystic nephroma; and thyroid gland neoplasia (multinodular goiter, adenomas, or differentiated thyroid cancer). Less commonly observed tumors are ciliary body medulloepithelioma; botryoid-type embryonal rhabdomyosarcoma of the cervix or other sites; nasal chondromesenchymal hamartoma; renal sarcoma; pituitary blastoma; and pineoblastoma. Novel phenotypes continue to be discovered. The majority of tumors in families with a DICER1 germline pathogenic variant occur in individuals younger than age 40 years. PPB, a neoplasm that arises during lung development or shortly after birth, typically presents in infants and children younger than age six years. Age of onset of ovarian sex cord-stromal tumors is not well defined. CN presents in children younger than age four years.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 11, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 14:95113197

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 11, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 14:95113197

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: LAMB2
Variant: c.2673C>T
(p.Gly891=)
rsID: rs144092322
Ref Allele: G
Alt Allele: A
Freq: 0.8099%rare
CADD: 6.579

ClinVar Submissions (3)

- Nephrotic syndrome, type 5, with or without ocular abnormalities, Autosomal recessive

  ### Nephrotic syndrome, type 5, with or without ocular abnormalities

  Nephrotic syndrome type 5 is an autosomal recessive disorder characterized by very early onset of progressive renal failure manifest as proteinuria with consecutive edema starting in utero or within the first 3 months of life. A subset of patients may develop mild ocular anomalies, such as myopia, nystagmus, and strabismus (summary by Hasselbacher et al., 2006). Mutation in the LAMB2 gene can also cause Pierson syndrome (609049), which is characterized by nephrotic syndrome, distinct ocular anomalies, namely microcoria, and neurodevelopmental delay. For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome, see NPHS1 (256300).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 10, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 3:49125300

- Pierson syndrome, Autosomal recessive

  ### Pierson syndrome

  Pierson syndrome is an autosomal recessive disorder comprising congenital nephrotic syndrome with diffuse mesangial sclerosis and distinct ocular abnormalities, including microcoria and hypoplasia of the ciliary and pupillary muscles, as well as other anomalies. Many patients die early, and those who survive tend to show neurodevelopmental delay and visual loss (summary by Zenker et al., 2004). Mutations in the LAMB2 gene also cause nephrotic syndrome type 5 with or without mild ocular anomalies (NPHS5; 614199).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 10, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 3:49125300

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 10, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 3:49125300

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 10, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 3:49125300

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: DLD
Variant: c.1422A>C
(p.Gly474=)
rsID: rs34453495
Ref Allele: A
Alt Allele: C
Freq: 0.8497%rare
CADD: 14.67

ClinVar Submissions (3)

- Maple syrup urine disease, type 3

  ### Maple syrup urine disease, type 3

  The phenotypes of dihydrolipoamide dehydrogenase (DLD) deficiency are an overlapping continuum that ranges from early-onset neurologic manifestations to adult-onset isolated liver involvement. Early-onset DLD deficiency typically manifests as a hypotonic infant with lactic acidosis. Affected infants frequently do not survive their initial metabolic decompensation, or die within the first few years of life during a recurrent metabolic decompensation. Children who live beyond the first two to three years frequently exhibit growth deficiencies and residual neurologic deficits (intellectual disability, spasticity, ataxia, and seizures). In contrast, isolated liver involvement can present as early as the neonatal period and as late as the third decade. Evidence of liver injury/failure is preceded by nausea and emesis and frequently associated with encephalopathy and/or coagulopathy. Acute metabolic episodes are frequently associated with lactate elevations, hyperammonemia, and hepatomegaly. With resolution of the acute episodes patients frequently return to baseline with no residual neurologic deficit or intellectual disability. Liver failure can result in death, even in those with late-onset disease.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 06, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 7:107919057

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 06, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 7:107919057

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 06, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 7:107919057

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

AC

Gene: RUNX1
Variant: c.*1466G>A
rsID: rs144796880
Ref Allele: C
Alt Allele: T
Freq: 0.8521%rare
CADD: 8.621

ClinVar Submissions (1)

- Familial platelet disorder with associated myeloid malignancy, Autosomal dominant

  ### Familial platelet disorder with associated myeloid malignancy

  Disease that is characterised by moderate thrombocytopenia, abnormal platelet function and the propensity to develop myeloid malignancies, in particular acute myelogenous leukaemia. The prevalence is unknown but the disease has been reported in less than 20 families. Causative mutations have been identified in the RUNX1 gene (also known as AML1 or CBFA2; chromosome 21q22.3) in most of the analysed families. The condition is inherited as an autosomal dominant trait.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 21:34790669

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CT

Gene: STX16
Variant: c.*1863C>A
rsID: rs141875151
Ref Allele: C
Alt Allele: A
Freq: 0.8673%rare
CADD: 1.461

ClinVar Submissions (1)

- Pseudohypoaldosteronism type 1 autosomal dominant, Autosomal dominant

  ### Pseudohypoaldosteronism type 1 autosomal dominant

  Autosomal dominant pseudohypoaldosteronism type I is characterized by salt wasting resulting from renal unresponsiveness to mineralocorticoids. Patients may present with neonatal renal salt wasting with hyperkalaemic acidosis despite high aldosterone levels. These patients improve with age and usually become asymptomatic without treatment. Some adult patients with the disorder may have elevated aldosterone levels, but no history of clinical disease. This observation suggests that only those infants whose salt homeostasis is stressed by intercurrent illness and volume depletion develop clinically recognized PHA I (summary by Geller et al., 1998). Autosomal recessive pseudohypoaldosteronism type I (PHA1B; 264350), caused by mutation in any one of 3 genes encoding the epithelial sodium channel (ENaC), is a similar but more severe systemic disorder with persistence into adulthood.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 20:58678154

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CA

Gene: PMS2
Variant: c.1789A>T
(p.Thr597Ser)
rsID: rs1805318
Ref Allele: T
Alt Allele: A
Freq: 0.8808%rare
CADD: 0.402

ClinVar Submissions (16)

- Hereditary cancer-predisposing syndrome

  ### Hereditary cancer-predisposing syndrome

  The condition of a pattern of malignancies within a family, but not every individual's necessarily having the same neoplasm. Characteristically the tumor tends to occur at an earlier than average age, individuals may have more than one primary tumor, the tumors may be multicentric, usually more than 25 percent of the individuals in direct lineal descent from the proband are affected, and the cancer predisposition in these families behaves as an autosomal dominant trait with about 60 percent penetrance.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 16, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 16
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 7:5986976

- Hereditary nonpolyposis colon cancer

  ### Hereditary nonpolyposis colon cancer

  A group of autosomal-dominant inherited diseases in which COLON CANCER arises in discrete adenomas. Unlike FAMILIAL POLYPOSIS COLI with hundreds of polyps, hereditary nonpolyposis colorectal neoplasms occur much later, in the fourth and fifth decades. HNPCC has been associated with germline mutations in mismatch repair (MMR) genes. It has been subdivided into Lynch syndrome I or site-specific colonic cancer, and LYNCH SYNDROME II which includes extracolonic cancer.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 16, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 16
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 7:5986976

- Hereditary nonpolyposis colorectal cancer type 4, Autosomal dominant

  ### Hereditary nonpolyposis colorectal cancer type 4

  Lynch syndrome, often called hereditary nonpolyposis colorectal cancer (HNPCC), is an inherited disorder that increases the risk of many types of cancer, particularly cancers of the colon (large intestine) and rectum, which are collectively referred to as colorectal cancer. People with Lynch syndrome also have an increased risk of cancers of the stomach, small intestine, liver, gallbladder ducts, upper urinary tract, brain, and skin. Additionally, women with this disorder have a high risk of cancer of the ovaries and lining of the uterus (the endometrium). People with Lynch syndrome may occasionally have noncancerous (benign) growths (polyps) in the colon, called colon polyps. In individuals with this disorder, colon polyps occur earlier but not in greater numbers than they do in the general population.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 16, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 16
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 7:5986976

- Lynch syndrome I, Autosomal dominant

  ### Lynch syndrome I

  Lynch syndrome is characterized by an increased risk for colorectal cancer (CRC) and cancers of the endometrium, stomach, ovary, small bowel, hepatobiliary tract, urinary tract, brain, and skin. In individuals with Lynch syndrome the following lifetime risks for cancer are seen: CRC: 52%-82% (mean age at diagnosis 44-61 years). Endometrial cancer in females: 25%-60% (mean age at diagnosis 48-62 years). Gastric cancer: 6%-13% (mean age at diagnosis 56 years). Ovarian cancer: 4%-12% (mean age at diagnosis 42.5 years; ~30% are diagnosed < age 40 years). The risk for other Lynch syndrome-related cancers is lower, though substantially increased over general population rates.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 16, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 16
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 7:5986976

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 16, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 16
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 7:5986976

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 16, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 16
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 7:5986976

Expert Reviewed Benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (18)

Hetero

TA

Gene: HBA1
Variant: c.*46C>A
rsID: rs141514155
Ref Allele: C
Alt Allele: A
Freq: 0.8824%rare
CADD: 4.591

ClinVar Submissions (2)

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 19, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 16:177457

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 19, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 16:177457

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CA

Gene: ANKH
Variant: c.*4219T>C
rsID: rs147322366
Ref Allele: A
Alt Allele: G
Freq: 0.884%rare
CADD: 0.821

ClinVar Submissions (1)

- Chondrocalcinosis

  ### Chondrocalcinosis

  Presence of CALCIUM PYROPHOSPHATE in the connective tissues such as the cartilaginous structures of joints. When accompanied by GOUT-like symptoms, it is referred to as pseudogout.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:14706978

- Craniometaphyseal dysplasia, Autosomal dominant

  ### Craniometaphyseal dysplasia

  Craniometadiaphyseal dysplasia (CRMDD) is characterized clinically by macrocephaly with frontal prominence, dental hypoplasia, and increased bone fragility. Diagnostic radiologic features include thin bones in the superior part of calvaria with prominent wormian bones, diaphyseal widening of the long tubular bones in early childhood with wide undermineralized metaphyses in older individuals, widened ribs and clavicles, and broadening of short tubular bones with increased transparency and thin cortices (summary by Dhar et al., 2010).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:14706978

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

AG

Gene: EPAS1
Variant: c.-140G>A
rsID: rs147597862
Ref Allele: G
Alt Allele: A
Freq: 0.9031%rare
CADD: 16.83

ClinVar Submissions (1)

- Familial erythrocytosis

  ### Familial erythrocytosis

  Polycythemia that occurs in groups of related individuals.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:46297772

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: PKD1
Variant: c.6598C>T
(p.Arg2200Cys)
rsID: rs140869992
Ref Allele: G
Alt Allele: A
Freq: 0.9381%rare
CADD: 23.1

ClinVar Submissions (5)

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 28, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 16:2108569

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 28, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 16:2108569

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OpenSNP
- PubMed (5)

Hetero

GA

Gene: SKI
Variant: c.456C>T
(p.Arg152=)
rsID: rs149898447
Ref Allele: C
Alt Allele: T
Freq: 0.9469%rare
CADD: 15.97

ClinVar Submissions (4)

- Cardiovascular phenotype

  ### Cardiovascular phenotype

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 26, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 1:2229222

- Shprintzen-Goldberg syndrome, Autosomal dominant

  ### Shprintzen-Goldberg syndrome

  Shprintzen-Goldberg syndrome (SGS) is characterized by: craniosynostosis of the coronal, sagittal, or lambdoid sutures; dolichocephaly; distinctive craniofacial features; skeletal changes (dolichostenomelia, arachnodactyly, camptodactyly, pes planus, pectus excavatum or carinatum, scoliosis, joint hypermobility or contractures and C1/C2 spine malformation); neurologic abnormalities; intellectual disability; and brain anomalies (hydrocephalus, dilatation of the lateral ventricles, and Chiari 1 malformation). Cardiovascular anomalies may include mitral valve prolapse, mitral regurgitation/incompetence, aortic regurgitation, and aortic root dilatation. Minimal subcutaneous fat, abdominal wall defects, myopia, and cryptorchidism in males are also characteristic findings.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 26, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 1:2229222

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 26, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 1:2229222

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: TMEM70
Variant: c.580G>A
(p.Val194Met)
rsID: rs77410280
Ref Allele: G
Alt Allele: A
Freq: 0.9533%rare
CADD: 21

ClinVar Submissions (3)

- Nuclearly-encoded mitochondrial complex V (ATP synthase) deficiency 2, Autosomal recessive

  ### Nuclearly-encoded mitochondrial complex V (ATP synthase) deficiency 2

  Mitochondrial complex V deficiency is a shortage (deficiency) of a protein complex called complex V or a loss of its function. Complex V is found in cell structures called mitochondria, which convert the energy from food into a form that cells can use. Complex V is the last of five mitochondrial complexes that carry out a multistep process called oxidative phosphorylation, through which cells derive much of their energy.Mitochondrial complex V deficiency can cause a wide variety of signs and symptoms affecting many organs and systems of the body, particularly the nervous system and the heart. The disorder can be life-threatening in infancy or early childhood. Affected individuals may have feeding problems, slow growth, low muscle tone (hypotonia), extreme fatigue (lethargy), and developmental delay. They tend to develop elevated levels of lactic acid in the blood (lactic acidosis), which can cause nausea, vomiting, weakness, and rapid breathing. High levels of ammonia in the blood (hyperammonemia) can also occur in affected individuals, and in some cases result in abnormal brain function (encephalopathy) and damage to other organs.Another common feature of mitochondrial complex V deficiency is hypertrophic cardiomyopathy. This condition is characterized by thickening (hypertrophy) of the heart (cardiac) muscle that can lead to heart failure. People with mitochondrial complex V deficiency may also have a characteristic pattern of facial features, including a high forehead, curved eyebrows, outside corners of the eyes that point downward (downslanting palpebral fissures), a prominent bridge of the nose, low-set ears, thin lips, and a small chin (micrognathia).Some people with mitochondrial complex V deficiency have groups of signs and symptoms that are classified as a specific syndrome. For example, mitochondrial complex V deficiency can cause a condition called neuropathy, ataxia, and retinitis pigmentosa (NARP). NARP causes a variety of signs and symptoms chiefly affecting the nervous system. Beginning in childhood or early adulthood, most people with NARP experience numbness, tingling, or pain in the arms and legs (sensory neuropathy); muscle weakness; and problems with balance and coordination (ataxia). Many affected individuals also have cognitive impairment and an eye disorder called retinitis pigmentosa that causes vision loss.A condition called Leigh syndrome can also be caused by mitochondrial complex V deficiency. Leigh syndrome is characterized by progressive loss of mental and movement abilities (developmental or psychomotor regression) and typically results in death within 2 to 3 years after the onset of symptoms. Both NARP and Leigh syndrome can also have other causes.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 27, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 8:73981418

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 27, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 8:73981418

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 27, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 8:73981418

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GA

Gene: DNMT1
Variant: c.1782A>G
(p.Thr594=)
rsID: rs721186
Ref Allele: T
Alt Allele: C
Freq: 0.9549%rare
CADD: 4.02

ClinVar Submissions (2)

- Dementia, Deafness, and Sensory Neuropathy

  ### Dementia, Deafness, and Sensory Neuropathy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 19:10154636

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 19:10154636

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (5)

Hetero

TC

Gene: IFT122
Variant: c.2096A>C
(p.Glu699Ala)
rsID: rs144397126
Ref Allele: A
Alt Allele: C
Freq: 0.9588%rare
CADD: 22.4

ClinVar Submissions (1)

- Cranioectodermal dysplasia

  ### Cranioectodermal dysplasia

  Cranioectodermal dysplasia (CED), a ciliopathy also known as Sensenbrenner syndrome, is a multisystem disorder with skeletal involvement (narrow thorax, shortened proximal limbs, and brachydactyly), ectodermal features (widely-spaced hypoplastic teeth, hypodontia, sparse hair, skin laxity, abnormal nails), joint laxity, growth retardation, and characteristic facial features (frontal bossing, low-set simple ears, high forehead, telecanthus/epicanthus, full cheeks, everted lower lip). Most affected children develop nephronophthisis that often leads to end-stage renal disease (ESRD) in infancy or childhood, a major cause of morbidity and mortality. Hepatic fibrosis and retinal dystrophy, other manifestations of ciliopathies, are also observed. Dolichocephaly, often secondary to sagittal craniosynostosis, is a primary manifestation that distinguishes CED from most other ciliopathies. Brain malformations and developmental delay may also occur.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 3:129488348

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

AC

Gene: STAT1
Variant: c.*535C>T
rsID: rs41476445
Ref Allele: G
Alt Allele: A
Freq: 0.9764%rare
CADD: 7.967

ClinVar Submissions (1)

- Familial Atypical Mycobacteriosis, Autosomal Dominant

  ### Familial Atypical Mycobacteriosis, Autosomal Dominant

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:190970168

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: SH3BP2
Variant: c.*4834G>A
rsID: rs147679025
Ref Allele: G
Alt Allele: A
Freq: 0.9819%rare
CADD: 2.592

ClinVar Submissions (1)

- Fibrous dysplasia of jaw, Autosomal dominant

  ### Fibrous dysplasia of jaw

  Cherubism is a childhood-onset, autoinflammatory bone disease characterized by bilateral and symmetric proliferative fibroosseous lesions limited to the mandible and maxilla. The enlargement is usually symmetric in nature. The phenotype ranges from no clinical manifestations to severe mandibular and maxillary overgrowth with respiratory, vision, speech, and swallowing problems. In most affected persons, teeth are displaced, unerupted, unformed, or absent, or may appear to be floating in cystlike spaces; malocclusion, premature exfoliation of deciduous teeth, and root resorption have also been reported. The course and duration of the active process of bone destruction varies between affected individuals; the onset is usually in early childhood, and typically new lesions can occur until puberty. Regression of the lesions occurs as they become filled with bone and remodel during the second and third decade of life. By age 30 years, the facial abnormalities associated with cherubism are not usually recognizable and residual deformity of the jaws is rare. Typically, cherubism is an isolated benign condition; the affected person has normal intellectual skills and is without other physical anomalies.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 4:2838668

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GA

Gene: SKIV2L
Variant: c.2052C>T
(p.His684=)
rsID: rs61761946
Ref Allele: C
Alt Allele: T
Freq: 0.9827%rare
CADD: 10.18

ClinVar Submissions (1)

- Trichohepatoenteric syndrome

  ### Trichohepatoenteric syndrome

  Although the spectrum of phenotypic expression in trichohepatoenteric syndrome (THES) is broad, the characteristic features include intrauterine growth retardation, woolly hair, facial dysmorphism, intractable diarrhea in infancy requiring total parenteral nutrition, and immunodepression. Hepatic involvement contributes to the poor prognosis of affected patients (summary by Fabre et al., 2007). Genetic Heterogeneity of Trichohepatoenteric Syndrome Trichohepatoenteric syndrome-2 (THES2; 614602) is caused by mutation in the SKIV2L gene (600478) on chromosome 6p21.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 6:31965863

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CT

Gene: THBD
Variant: c.*1993T>C
rsID: rs3176136
Ref Allele: A
Alt Allele: G
Freq: 0.9891%rare
CADD: 5.085

ClinVar Submissions (1)

- Atypical hemolytic uremic syndrome

  ### Atypical hemolytic uremic syndrome

  Hemolytic-uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia, and renal failure caused by platelet thrombi in the microcirculation of the kidney and other organs. The onset of atypical HUS (aHUS) ranges from the neonatal period to adulthood. Genetic aHUS accounts for an estimated 60% of all aHUS. Individuals with genetic aHUS frequently experience relapse even after complete recovery following the presenting episode; 60% of genetic aHUS progresses to end-stage renal disease (ESRD).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 20:23045784

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

AG

## Uncommon Mutations

Below are uncommon mutations (frequency between 1% and 5%) found in ClinVar. The data presented has no guarantees of reporting accuracy. Heterozygous variants are repoted as yellow and homozygous variants as red. A red or yellow variant does not necessarily mean one has or carries a condition or disease. This is for research and educational purposes only.

Gene: KCNQ3
Variant: c.*3823G>A
rsID: rs17651980
Ref Allele: C
Alt Allele: T
Freq: 1.0011%uncommon
CADD: 0.26

ClinVar Submissions (1)

- Benign Neonatal Epilepsy

  ### Benign Neonatal Epilepsy

  A condition marked by recurrent seizures that occur during the first 4-6 weeks of life despite an otherwise benign neonatal course. Autosomal dominant familial and sporadic forms have been identified. Seizures generally consist of brief episodes of tonic posturing and other movements, apnea, eye deviations, and blood pressure fluctuations. These tend to remit after the 6th week of life. The risk of developing epilepsy at an older age is moderately increased in the familial form of this disorder. (Neurologia 1996 Feb;11(2):51-5)

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 8:132125439

- Benign familial neonatal seizures

  ### Benign familial neonatal seizures

  Benign familial neonatal seizures (BFNS) is a condition characterized by recurrent seizures in newborn babies. The seizures begin around day 3 of life and usually go away within 1 to 4 months. The seizures can involve only one side of the brain (focal seizures) or both sides (generalized seizures). Many infants with this condition have generalized tonic-clonic seizures (also known as grand mal seizures). This type of seizure involves both sides of the brain and affects the entire body, causing muscle rigidity, convulsions, and loss of consciousness.A test called an electroencephalogram (EEG) is used to measure the electrical activity of the brain. Abnormalities on an EEG test, measured during no seizure activity, can indicate a risk for seizures. However, infants with BFNS usually have normal EEG readings. In some affected individuals, the EEG shows a specific abnormality called the theta pointu alternant pattern. By age 2, most affected individuals who had EEG abnormalities have a normal EEG reading.Typically, seizures are the only symptom of BFNS, and most people with this condition develop normally. However, some affected individuals develop intellectual disability that becomes noticeable in early childhood. A small percentage of people with BFNS also have a condition called myokymia, which is an involuntary rippling movement of the muscles. In addition, in about 15 percent of people with BFNS, recurrent seizures (epilepsy) will come back later in life after the seizures associated with BFNS have gone away. The age that epilepsy begins is variable.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 8:132125439

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CT

Gene: OTOF
Variant: c.3470G>A
(p.Arg1157Gln)
rsID: rs56054534
Ref Allele: C
Alt Allele: T
Freq: 1.005%uncommon
CADD: 23.2

ClinVar Submissions (3)

- Deafness, autosomal recessive 9, Autosomal recessive

  ### Deafness, autosomal recessive 9

  OTOF-related deafness (DFNB9 nonsyndromic hearing loss) is characterized by two phenotypes: prelingual nonsyndromic hearing loss and, less frequently, temperature-sensitive nonsyndromic auditory neuropathy (TS-NSAN). The nonsyndromic hearing loss is bilateral severe-to-profound congenital deafness. In the first one or two years of life, OTOF-related deafness can appear to be an auditory neuropathy based on electrophysiologic testing in which auditory brain stem responses (ABRs) are absent and otoacoustic emissions (OAEs) are present. However, with time OAEs disappear and electrophysiologic testing is more consistent with a cochlear defect. The distinction between auditory neuropathy and a cochlear defect is important as cochlear implants may be of marginal value in persons with auditory neuropathy but have been shown to be effective for individuals with OTOF-related deafness. TS-NSAN is characterized by normal-to-mild hearing loss in the absence of fever and significant hearing loss ranging from severe to profound in the presence of fever. When the fever resolves, hearing returns to normal.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 30, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:26473506

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 30, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:26473506

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (5)

Hetero

CT

Gene: SCN2A
Variant: c.1785T>C
(p.Asp595=)
rsID: rs141815642
Ref Allele: T
Alt Allele: C
Freq: 1.0138%uncommon
CADD: 11.69

ClinVar Submissions (6)

- Benign familial neonatal-infantile seizures, Autosomal dominant

  ### Benign familial neonatal-infantile seizures

  Benign familial neonatal-infantile seizures is an autosomal dominant disorder in which afebrile seizures occur in clusters during the first year of life, without neurologic sequelae (Shevell et al., 1986). For a general phenotypic description and a discussion of genetic heterogeneity of benign familial infantile seizures, see BFIS1 (601764). BFIS1 has a slightly later onset than BFIS3, while benign neonatal seizures (see BFNS1, 121200) has a slightly earlier onset.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 03, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:165323269

- Benign familial neonatal-infantile seizures, Autosomal dominant

  ### Benign familial neonatal-infantile seizures

  Benign familial neonatal-infantile seizures is an autosomal dominant disorder in which afebrile seizures occur in clusters during the first year of life, without neurologic sequelae (Shevell et al., 1986). For a general phenotypic description and a discussion of genetic heterogeneity of benign familial infantile seizures, see BFIS1 (601764). BFIS1 has a slightly later onset than BFIS3, while benign neonatal seizures (see BFNS1, 121200) has a slightly earlier onset.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 03, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:165323269

- Early Infantile Epileptic Encephalopathy, Autosomal Dominant

  ### Early Infantile Epileptic Encephalopathy, Autosomal Dominant

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 03, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:165323269

- Early infantile epileptic encephalopathy 11, Autosomal dominant

  ### Early infantile epileptic encephalopathy 11

  Early infantile epileptic encephalopathy-11 is an autosomal dominant seizure disorder characterized by infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities (Ogiwara et al., 2009). For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 03, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:165323269

- History of neurodevelopmental disorder

  ### History of neurodevelopmental disorder

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 03, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:165323269

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 03, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:165323269

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (2)

Hetero

TC

Gene: ITGB4
Variant: c.4843+14C>T
rsID: rs78884789
Ref Allele: C
Alt Allele: T
Freq: 1.0289%uncommon
CADD: 0.112

ClinVar Submissions (1)

- Epidermolysis bullosa junctionalis with pyloric atresia, Autosomal recessive

  ### Epidermolysis bullosa junctionalis with pyloric atresia

  Epidermolysis bullosa with pyloric atresia (EB-PA) is characterized by fragility of the skin and mucous membranes, manifested by blistering with little or no trauma; congenital pyloric atresia; and ureteral and renal anomalies (dysplastic/multicystic kidney, hydronephrosis/hydroureter, ureterocele, duplicated renal collecting system, absent bladder). The course of EB-PA is usually severe and often lethal in the neonatal period. Most affected children succumb as neonates; those who survive may have severe blistering with formation of granulation tissue on the skin around the mouth, nose, fingers, and toes, and internally around the trachea. However, some affected individuals have little or no blistering later in life. Additional features shared by EB-PA and the other major forms of EB include congenital localized absence of skin (aplasia cutis congenita) affecting the extremities and/or head, milia, nail dystrophy, scarring alopecia, hypotrichosis, contractures, and dilated cardiomyopathy.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 17:75756873

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CT

Gene: SLC52A3
Variant: c.600C>T
(p.Pro200=)
rsID: rs16992990
Ref Allele: G
Alt Allele: A
Freq: 1.0417%uncommon
CADD: 0.165

ClinVar Submissions (3)

- Brown-Vialetto-Van Laere syndrome 1

  ### Brown-Vialetto-Van Laere syndrome 1

  Brown-Vialetto-Van Laere syndrome is a rare autosomal recessive neurologic disorder characterized by sensorineural hearing loss and a variety of cranial nerve palsies, usually involving the motor components of the seventh and ninth to twelfth (more rarely the third, fifth, and sixth) cranial nerves. Spinal motor nerves and, less commonly, upper motor neurons are sometimes affected, giving a picture resembling amyotrophic lateral sclerosis (ALS; 105400). The onset of the disease is usually in the second decade, but earlier and later onset have been reported. Hearing loss tends to precede the onset of neurologic signs, mostly progressive muscle weakness causing respiratory compromise. However, patients with very early onset may present with bulbar palsy and may not develop hearing loss until later. The symptoms, severity, and disease duration are variable (summary by Green et al., 2010). Genetic Heterogeneity of Brown-Vialetto-Van Laere Syndrome See also BVVLS2 (614707), caused by mutation in the SLC52A2 gene (607882) on chromosome 8q.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 23, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 20:763971

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 23, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 20:763971

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: ABCA4
Variant: c.6729+21C>T
rsID: rs1800699
Ref Allele: G
Alt Allele: A
Freq: 1.0624%uncommon
CADD: 0.136

ClinVar Submissions (2)

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: criteria provided, single submitter
  Number of Submitters: 2
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:93997840

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: criteria provided, single submitter
  Number of Submitters: 2
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:93997840

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (2)

Hetero

GA

Gene: LAMB3
Variant: c.1015T>C
(p.Tyr339His)
rsID: rs52814161
Ref Allele: A
Alt Allele: G
Freq: 1.0695%uncommon
CADD: 12.9

ClinVar Submissions (1)

- Epidermolysis bullosa, junctional

  ### Epidermolysis bullosa, junctional

  Junctional epidermolysis bullosa (JEB) is characterized by fragility of the skin and mucous membranes, manifest by blistering with little or no trauma. Blistering may be severe and granulation tissue can form on the skin around the oral and nasal cavities, fingers and toes, and internally around the upper airway. Blisters generally heal with no significant scarring. Broad classification of JEB includes JEB generalized severe and JEB generalized intermediate. In JEB generalized severe, blisters are present at birth or become apparent in the neonatal period. Congenital malformations of the urinary tract and bladder may also occur. In JEB generalized intermediate, the phenotype may be mild with blistering localized to hands, feet, knees, and elbows with or without renal or ureteral involvement. Some individuals never blister after the newborn period. Additional features shared by JEB and the other major forms of epidermolysis bullosa (EB) include congenital localized absence of skin (aplasia cutis congenita), milia, nail dystrophy, scarring alopecia, hypotrichosis, pseudosyndactyly, and other contractures.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 1:209629854

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

AG

Gene: COQ8A
Variant: c.1053C>T
(p.Gly351=)
rsID: rs55958233
Ref Allele: C
Alt Allele: T
Freq: 1.0799%uncommon
CADD: 0.07

ClinVar Submissions (4)

- Autosomal recessive cerebellar ataxia

  ### Autosomal recessive cerebellar ataxia

  Autosomal recessive cerebellar ataxias (ARCA) are a heterogeneous group of rare neurological disorders involving both the central and peripheral nervous system (and in some cases other systems and organs), and characterized by degeneration or abnormal development of the cerebellum and spinal cord and, in most cases, early onset occurring before the age of 20 years.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:226983007

- Coenzyme Q10 deficiency, Spinocerebellar Ataxia Type

  ### Coenzyme Q10 deficiency, Spinocerebellar Ataxia Type

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:226983007

- Coenzyme Q10 deficiency, primary, 4, Autosomal recessive

  ### Coenzyme Q10 deficiency, primary, 4

  Primary coenzyme Q10 (CoQ10) deficiency is usually associated with multisystem involvement, including neurologic manifestations such as fatal neonatal encephalopathy with hypotonia; a late-onset slowly progressive multiple-system atrophy-like phenotype (neurodegeneration with autonomic failure and various combinations of parkinsonism and cerebellar ataxia, and pyramidal dysfunction); and dystonia, spasticity, seizures, and intellectual disability. Steroid-resistant nephrotic syndrome (SRNS), the hallmark renal manifestation, is often the initial manifestation either as isolated renal involvement that progresses to end-stage renal disease (ESRD), or associated with encephalopathy (seizures, stroke-like episodes, severe neurologic impairment) resulting in early death. Hypertrophic cardiomyopathy (HCM), retinopathy or optic atrophy, and sensorineural hearing loss can also be seen.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:226983007

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:226983007

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:226983007

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CT

Gene: SERPINI1
Variant: c.838G>A
(p.Ala280Thr)
rsID: rs55872908
Ref Allele: G
Alt Allele: A
Freq: 1.1118%uncommon
CADD: 23.1

ClinVar Submissions (2)

- Encephalopathy, familial, with neuroserpin inclusion bodies, Autosomal dominant

  ### Encephalopathy, familial, with neuroserpin inclusion bodies

  Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is a disorder that causes progressive dysfunction of the brain (encephalopathy). It is characterized by a loss of intellectual functioning (dementia) and seizures. At first, affected individuals may have difficulty sustaining attention and concentrating. They may experience repetitive thoughts, speech, or movements. As the condition progresses, their personality changes and judgment, insight, and memory become impaired. Affected people lose the ability to perform the activities of daily living, and most eventually require comprehensive care.The signs and symptoms of FENIB vary in their severity and age of onset. In severe cases, the condition causes seizures and episodes of sudden, involuntary muscle jerking or twitching (myoclonus) in addition to dementia. These signs can appear as early as a person's teens. Less severe cases are characterized by a progressive decline in intellectual functioning beginning in a person's forties or fifties.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 31, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 3:167794781

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GA

Gene: COL6A3
Variant: c.768C>T
(p.Val256=)
rsID: rs79606264
Ref Allele: G
Alt Allele: A
Freq: 1.1141%uncommon
CADD: 9.144

ClinVar Submissions (6)

- Bethlem myopathy 1

  ### Bethlem myopathy 1

  Collagen type VI-related disorders represent a continuum of overlapping phenotypes with Bethlem myopathy at the mild end, Ullrich congenital muscular dystrophy (CMD) at the severe end, and two rare, less well-defined disorders – autosomal dominant limb-girdle muscular dystrophy and autosomal recessive myosclerosis myopathy – in between. Although Bethlem myopathy and Ullrich CMD were defined long before their molecular basis was known, they remain useful for clarification of prognosis and management. Bethlem myopathy, characterized by the combination of proximal muscle weakness and variable contractures, affects most frequently the long finger flexors, elbows, and ankles. Onset may be prenatal (characterized by decreased fetal movements), neonatal (hypotonia or torticollis), in early childhood (delayed motor milestones, muscle weakness, and contractures), or in adulthood (proximal weakness and Achilles tendon or long finger flexor contractures). Because of slow progression, more than two thirds of affected individuals over age 50 years rely on supportive means for outdoor mobility. Respiratory involvement is rare and appears to be related to more severe muscle weakness in later life. Ullrich CMD is characterized by congenital weakness and hypotonia, proximal joint contractures, and striking hyperlaxity of distal joints. Some affected children acquire the ability to walk independently; however, progression of the disease often results in later loss of ambulation. Early and severe respiratory involvement may require ventilatory support in the first or second decade of life.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 03, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:237388126

- Collagen VI-related myopathy

  ### Collagen VI-related myopathy

  Collagen type VI-related disorders represent a continuum of overlapping phenotypes with Bethlem myopathy at the mild end, Ullrich congenital muscular dystrophy (CMD) at the severe end, and two rare, less well-defined disorders – autosomal dominant limb-girdle muscular dystrophy and autosomal recessive myosclerosis myopathy – in between. Although Bethlem myopathy and Ullrich CMD were defined long before their molecular basis was known, they remain useful for clarification of prognosis and management. Bethlem myopathy, characterized by the combination of proximal muscle weakness and variable contractures, affects most frequently the long finger flexors, elbows, and ankles. Onset may be prenatal (characterized by decreased fetal movements), neonatal (hypotonia or torticollis), in early childhood (delayed motor milestones, muscle weakness, and contractures), or in adulthood (proximal weakness and Achilles tendon or long finger flexor contractures). Because of slow progression, more than two thirds of affected individuals over age 50 years rely on supportive means for outdoor mobility. Respiratory involvement is rare and appears to be related to more severe muscle weakness in later life. Ullrich CMD is characterized by congenital weakness and hypotonia, proximal joint contractures, and striking hyperlaxity of distal joints. Some affected children acquire the ability to walk independently; however, progression of the disease often results in later loss of ambulation. Early and severe respiratory involvement may require ventilatory support in the first or second decade of life.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 03, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:237388126

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 03, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:237388126

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (2)

Hetero

GA

Gene: KCNA1
Variant: c.*1522C>G
rsID: rs140297443
Ref Allele: C
Alt Allele: G
Freq: 1.1261%uncommon
CADD: 16.8

ClinVar Submissions (1)

- Episodic ataxia

  ### Episodic ataxia

  Periodic spells of incoordination and imbalance, that is, episodes of ataxia typically lasting from 10 minutes to several hours or days.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 12:4914388

- Myokymia

  ### Myokymia

  A disorder characterized by involuntary and irregular muscle contractions not associated with muscle weakness or atrophy. It most often affects facial muscles. It may be localized or generalized.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 12:4914388

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CG

Gene: PRPF8
Variant: c.-79C>T
rsID: rs74635192
Ref Allele: G
Alt Allele: A
Freq: 1.1277%uncommon
CADD: 16.33

ClinVar Submissions (1)

- Retinitis Pigmentosa, Dominant

  ### Retinitis Pigmentosa, Dominant

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 17:1684847

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: DST
Variant: c.3234G>A
(p.Arg1078=)
rsID: rs41271870
Ref Allele: C
Alt Allele: T
Freq: 1.1444%uncommon
CADD: 8.628

ClinVar Submissions (1)

- Epidermolysis bullosa simplex, autosomal recessive 2, Autosomal recessive

  ### Epidermolysis bullosa simplex, autosomal recessive 2

  EBSB2 is a mild autosomal recessive dermatologic disorder characterized by trauma-induced blistering mainly occurring on the feet and ankles. Ultrastructural analysis of skin biopsy shows abnormal hemidesmosomes with poorly formed inner plaques (summary by Liu et al., 2012).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 04, 2018
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 6:56624614

- Neuropathy, hereditary sensory and autonomic, type VI, Autosomal recessive

  ### Neuropathy, hereditary sensory and autonomic, type VI

  Hereditary sensory and autonomic neuropathy type VI is a severe autosomal recessive disorder characterized by neonatal hypotonia, respiratory and feeding difficulties, lack of psychomotor development, and autonomic abnormalities including labile cardiovascular function, lack of corneal reflexes leading to corneal scarring, areflexia, and absent axonal flare response after intradermal histamine injection (summary by Edvardson et al., 2012). For a discussion of genetic heterogeneity of hereditary sensory and autonomic neuropathy, see HSAN1 (162400).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 04, 2018
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 6:56624614

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CT

Gene: GLIS3
Variant: c.1071C>A
(p.Asp357Glu)
rsID: rs148199056
Ref Allele: G
Alt Allele: T
Freq: 1.1603%uncommon
CADD: 19.87

ClinVar Submissions (3)

- Diabetes mellitus, neonatal, with congenital hypothyroidism, Autosomal recessive

  ### Diabetes mellitus, neonatal, with congenital hypothyroidism

  Neonatal diabetes mellitus with congenital hypothyroidism (NDH) syndrome is characterized by intrauterine growth retardation and onset of nonimmune diabetes mellitus within the first few weeks of life. Other features include renal parenchymal disease, primarily renal cystic dysplasia, and hepatic disease, with hepatitis in some patients and hepatic fibrosis and cirrhosis in others. Facial dysmorphism, when present, consistently involves low-set ears, epicanthal folds, flat nasal bridge, long philtrum, and thin upper lip. Most patients exhibit developmental delay (Dimitri et al., 2015).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 18, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 9:4117942

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 18, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 9:4117942

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

GT

Gene: TNXB
Variant: c.12372C>T
(p.Asp4124=)
rsID: rs11755562
Ref Allele: G
Alt Allele: A
Freq: 1.1747%uncommon
CADD: 1.326

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 6:32042103

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: ZMPSTE24
Variant: c.-211-743G>C
rsID: rs147867849
Ref Allele: G
Alt Allele: C
Freq: 1.1938%uncommon
CADD: 5.307

ClinVar Submissions (1)

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: no assertion provided
  Number of Submitters: 1
  Clinical Significance: not provided
  Assembly: GRCh38
  Chromosome/Position: 1:40257318

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

GC

Gene: PNPLA1
Variant: c.1179T>A
(p.Tyr393Ter)
rsID: rs45621032
Ref Allele: T
Alt Allele: A
Freq: 1.1986%uncommon
CADD: 33

ClinVar Submissions (2)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 14, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 6:36306371

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

TA

Gene: MEN1
Variant: c.512G>A
(p.Arg171Gln)
rsID: rs607969
Ref Allele: C
Alt Allele: T
Freq: 1.2288%uncommon
CADD: 23.4

ClinVar Submissions (13)

- Hereditary cancer-predisposing syndrome

  ### Hereditary cancer-predisposing syndrome

  The condition of a pattern of malignancies within a family, but not every individual's necessarily having the same neoplasm. Characteristically the tumor tends to occur at an earlier than average age, individuals may have more than one primary tumor, the tumors may be multicentric, usually more than 25 percent of the individuals in direct lineal descent from the proband are affected, and the cancer predisposition in these families behaves as an autosomal dominant trait with about 60 percent penetrance.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 22, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 13
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 11:64808033

- Multiple endocrine neoplasia

  ### Multiple endocrine neoplasia

  A group of autosomal dominant diseases characterized by the combined occurrence of tumors involving two or more ENDOCRINE GLANDS that secrete PEPTIDE HORMONES or AMINES. These neoplasias are often benign but can be malignant. They are classified by the endocrine glands involved and the degree of aggressiveness. The two major forms are MEN1 and MEN2 with gene mutations on CHROMOSOME 11 and CHROMOSOME 10, respectively.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 22, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 13
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 11:64808033

- Multiple endocrine neoplasia, type 1, Autosomal dominant

  ### Multiple endocrine neoplasia, type 1

  Multiple endocrine neoplasia type 1 (MEN1) syndrome includes varying combinations of more than 20 endocrine and non-endocrine tumors. Endocrine tumors become evident either by overproduction of hormones by the tumor or by growth of the tumor itself. Parathyroid tumors are the main MEN1-associated endocrinopathy; onset in 90% of individuals is between ages 20 and 25 years with hypercalcemia evident by age 50 years; hypercalcemia causes lethargy, depression, confusion, anorexia, constipation, nausea, vomiting, diuresis, dehydration, hypercalciuria, kidney stones, increased bone resorption/fracture risk, hypertension, and shortened QT interval. Pituitary tumors include prolactinoma (the most common), which manifests as oligomenorrhea/amenorrhea and galactorrhea in females and sexual dysfunction in males. Well-differentiated endocrine tumors of the gastro-entero-pancreatic (GEP) tract can manifest as Zollinger-Ellison syndrome (gastrinoma); hypoglycemia (insulinoma); hyperglycemia, anorexia, glossitis, anemia, diarrhea, venous thrombosis, and skin rash (glucagonoma); and watery diarrhea, hypokalemia, and achlorhydria syndrome (vasoactive intestinal peptide [VIP]-secreting tumor). Carcinoid tumors are non-hormone-secreting and can manifest as a large mass after age 50 years. Adrenocortical tumors can be associated with primary hypercortisolism or hyperaldosteronism. Non-endocrine tumors include facial angiofibromas, collagenomas, lipomas, meningiomas, ependymomas, and leiomyomas.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 22, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 13
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 11:64808033

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 22, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 13
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 11:64808033

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 22, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 13
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 11:64808033

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (6)

Hetero

CT

Gene: SMAD9
Variant: c.*2905T>C
rsID: rs118015060
Ref Allele: A
Alt Allele: G
Freq: 1.2296%uncommon
CADD: 6.88

ClinVar Submissions (1)

- Primary pulmonary hypertension, Autosomal dominant

  ### Primary pulmonary hypertension

  Pulmonary arterial hypertension (PAH) is characterized by widespread obstruction and obliteration of the smallest pulmonary arteries. When a sufficient number of vessels are occluded, the resistance to blood flow through the lungs increases, and the right ventricle attempts to compensate by generating higher pressure to maintain pulmonary blood flow. When the right ventricle can no longer compensate for the increased resistance, progressive heart failure ensues. Initial symptoms include dyspnea (60%), fatigue (19%), syncope (8%), chest pain (7%), palpitations (5%), and leg edema (3%). All ages are affected, but the mean age at diagnosis is 36 years. Mean survival after diagnosis is 2.8 years; current therapy does improve clinical function but has modest effect on survival. The term "heritable PAH" (HPAH) includes familial PAH (PAH that occurs in two or more family members) and simplex PAH (i.e., a single occurrence in a family) when a pathogenic variant has been identified. Most heritable PAH (75%) is caused by a pathogenic variant in BMPR2; pathogenic variants in other genes (i.e., ACVRL1, KCNK3, CAV1, SMAD9, BMPR1B) are considerably less common (1%-3%). HPAH has identical symptoms, signs, and histology as PAH of unknown cause. The time from onset of symptoms to diagnosis may be shorter in individuals with familial PAH, possibly because of familial awareness of the disease. Three retrospective studies suggest that persons with PAH who have a BMPR2 pathogenic variant exhibit more severe disease.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 13:36845771

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

AG

Gene: MIP
Variant: c.-10C>A
rsID: rs61759527
Ref Allele: G
Alt Allele: T
Freq: 1.2599%uncommon
CADD: 18.77

ClinVar Submissions (1)

- Cataract

  ### Cataract

  A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule. [HPO:probinson]

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 12:56454623

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (2)

Hetero

GT

Gene: UMPS
Variant: c.*993A>T
rsID: rs74704429
Ref Allele: A
Alt Allele: T
Freq: 1.2615%uncommon
CADD: 2.199

ClinVar Submissions (1)

- Orotic aciduria

  ### Orotic aciduria

  Orotic aciduria is a rare autosomal recessive disorder characterized by megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and mental retardation. These features respond to appropriate pyrimidine replacement therapy, and most cases appear to have a good prognosis. A minority of cases have additional features, particularly congenital malformations and immune deficiencies, which may adversely affect this prognosis (summary by Webster et al., 2001). Bailey (2009) stated that only 2 cases of orotic aciduria without megaloblastic anemia (OAWA) had been reported.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 3:124745077

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

AT

Gene: SLC4A1
Variant: c.16-14G>A
rsID: rs145502796
Ref Allele: C
Alt Allele: T
Freq: 1.2655%uncommon
CADD: 0.829

ClinVar Submissions (2)

- Distal Renal Tubular Acidosis, Dominant

  ### Distal Renal Tubular Acidosis, Dominant

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 17:44262740

- Hemolytic anemia

  ### Hemolytic anemia

  A condition of inadequate circulating red blood cells (ANEMIA) or insufficient HEMOGLOBIN due to premature destruction of red blood cells (ERYTHROCYTES).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 17:44262740

- Spherocytosis, Dominant

  ### Spherocytosis, Dominant

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 17:44262740

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 17:44262740

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: ABCC8
Variant: c.3329+6C>T
rsID: rs113873225
Ref Allele: G
Alt Allele: A
Freq: 1.2678%uncommon
CADD: 0.266

ClinVar Submissions (5)

- Hyperinsulinism, Dominant/Recessive

  ### Hyperinsulinism, Dominant/Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 06, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:17406616

- Permanent neonatal diabetes mellitus, Autosomal dominant

  ### Permanent neonatal diabetes mellitus

  Permanent neonatal diabetes mellitus (PNDM) is characterized by the onset of hyperglycemia within the first six months of life (mean age: 7 weeks; range: birth to 26 weeks). The diabetes mellitus is associated with partial or complete insulin deficiency. Clinical manifestations at the time of diagnosis include intrauterine growth retardation, hyperglycemia, glycosuria, osmotic polyuria, severe dehydration, and failure to thrive. Therapy with insulin corrects the hyperglycemia and results in dramatic catch-up growth. The course of PNDM varies by genotype.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 06, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:17406616

- Transient Neonatal Diabetes, Dominant

  ### Transient Neonatal Diabetes, Dominant

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 06, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:17406616

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 06, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:17406616

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (4)

Hetero

GA

Gene: TFAP2B
Variant: c.252C>T
(p.Asp84=)
rsID: rs75279409
Ref Allele: C
Alt Allele: T
Freq: 1.2933%uncommon
CADD: 12.89

ClinVar Submissions (1)

- Char syndrome, Autosomal dominant

  ### Char syndrome

  Char syndrome is characterized by the triad of typical facial features, patent ductus arteriosus (PDA), and aplasia or hypoplasia of the middle phalanges of the fifth fingers. Typical facial features are flat midface, flat nasal bridge and broad flat nasal tip, wide-set eyes, downslanting palpebral fissures, mild ptosis, short philtrum resulting in a triangular mouth, and thickened (patulous) everted lips.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 6:50823577

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CT

Gene: CREBBP
Variant: c.6621A>G
(p.Gln2207=)
rsID: rs55960450
Ref Allele: T
Alt Allele: C
Freq: 1.2965%uncommon
CADD: 8.882

ClinVar Submissions (5)

- History of neurodevelopmental disorder

  ### History of neurodevelopmental disorder

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 19, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 16:3728426

- Rubinstein-Taybi syndrome 1, Autosomal dominant

  ### Rubinstein-Taybi syndrome 1

  Rubinstein-Taybi syndrome (RSTS) is characterized by distinctive facial features, broad and often angulated thumbs and great toes, short stature, and moderate to severe intellectual disability. The characteristic craniofacial features are downslanted palpebral fissures, low-hanging columella, high palate, grimacing smile, and talon cusps. Prenatal growth is often normal; however, height, weight, and head circumference percentiles rapidly drop in the first few months of life. Obesity may occur in childhood or adolescence. IQ scores range from 25 to 79; average IQ is between 36 and 51. Other variable findings are coloboma, cataract, congenital heart defects, renal abnormalities, and cryptorchidism.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 19, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 16:3728426

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 19, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 16:3728426

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (3)

Hetero

TC

Gene: KCND3
Variant: c.669G>C
(p.Ser223=)
rsID: rs17215423
Ref Allele: C
Alt Allele: G
Freq: 1.3045%uncommon
CADD: 5.166

ClinVar Submissions (3)

- Cardiovascular phenotype

  ### Cardiovascular phenotype

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 05, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 1:111982058

- Spinocerebellar ataxia 19, Autosomal dominant

  ### Spinocerebellar ataxia 19

  The hereditary ataxias are a group of genetic disorders characterized by slowly progressive incoordination of gait and often associated with poor coordination of hands, speech, and eye movements. Frequently, atrophy of the cerebellum occurs. In this GeneReview the hereditary ataxias are categorized by mode of inheritance and gene (or chromosome locus) in which pathogenic variants occur.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 05, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 1:111982058

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 05, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 1:111982058

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CG

Gene: RTEL1
Variant: c.3173C>A
(p.Pro1058His)
rsID: rs115610405
Ref Allele: C
Alt Allele: A
Freq: 1.3164%uncommon
CADD: 14.19

ClinVar Submissions (1)

- Dyskeratosis congenita, autosomal recessive, 5, Autosomal dominant

  ### Dyskeratosis congenita, autosomal recessive, 5

  Dyskeratosis congenita (DC), a telomere biology disorder, is characterized by a classic triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia. The classic triad may not be present in all individuals. People with DC are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML), solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include: abnormal pigmentation changes not restricted to the upper chest and neck, eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), and dental abnormalities (caries, periodontal disease, taurodauntism). Although most persons with DC have normal psychomotor development and normal neurologic function, significant developmental delay is present in the two variants in which additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome). Onset and progression of manifestations of DC vary: at the mild end of the spectrum are those who have only minimal physical findings with normal bone marrow function, and at the severe end are those who have the diagnostic triad and early-onset BMF.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 31, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 20:63694480

- Pulmonary fibrosis and/or bone marrow failure, telomere-related, 3, Autosomal dominant

  ### Pulmonary fibrosis and/or bone marrow failure, telomere-related, 3

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 31, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 20:63694480

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CA

Gene: COL6A2
Variant: c.*5C>T
rsID: rs76978157
Ref Allele: C
Alt Allele: T
Freq: 1.3212%uncommon
CADD: 0.045

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 21:46129496

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: RUNX1
Variant: c.*484T>C
rsID: rs147934675
Ref Allele: A
Alt Allele: G
Freq: 1.3268%uncommon
CADD: 8.103

ClinVar Submissions (1)

- Familial platelet disorder with associated myeloid malignancy, Autosomal dominant

  ### Familial platelet disorder with associated myeloid malignancy

  Disease that is characterised by moderate thrombocytopenia, abnormal platelet function and the propensity to develop myeloid malignancies, in particular acute myelogenous leukaemia. The prevalence is unknown but the disease has been reported in less than 20 families. Causative mutations have been identified in the RUNX1 gene (also known as AML1 or CBFA2; chromosome 21q22.3) in most of the analysed families. The condition is inherited as an autosomal dominant trait.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 21:34791651

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

AG

Gene: DTNBP1
Variant: c.889C>T
(p.His297Tyr)
rsID: rs16876571
Ref Allele: G
Alt Allele: A
Freq: 1.3316%uncommon
CADD: 0.632

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 21, 2013
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 6:15524448

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (3)

Hetero

GA

Gene: ANGPTL4
Variant: c.118G>A
(p.Glu40Lys)
rsID: rs116843064
Ref Allele: G
Alt Allele: A
Freq: 1.3411%uncommon
CADD: 32

ClinVar Submissions (1)

- Plasma triglyceride level quantitative trait locus, Autosomal dominant

  ### Plasma triglyceride level quantitative trait locus

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 05, 2012
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: association
  Assembly: GRCh38
  Chromosome/Position: 19:8364439
  OMIM Allelic Variant: 605910.0001

Insufficiently evaluated pathogenic — This dominant protective variant reduces the mean plasma triglyceride level by 15% in heterozygous carriers.

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (4)

Hetero

GA

Gene: CHD7
Variant: c.307T>A
(p.Ser103Thr)
rsID: rs41272435
Ref Allele: T
Alt Allele: A
Freq: 1.3491%uncommon
CADD: 20.9

ClinVar Submissions (10)

- CHARGE association, Autosomal dominant

  ### CHARGE association

  CHARGE is a mnemonic for coloboma, heart defects, choanal atresia, retarded growth and development, genital abnormalities, and ear anomalies. CHARGE syndrome is characterized by the following: Unilateral or bilateral coloboma of the iris, retina-choroid, and/or disc with or without microphthalmos (80%-90% of individuals). Unilateral or bilateral choanal atresia or stenosis (50%-60%). Cranial nerve dysfunction resulting in hyposmia or anosmia, unilateral or bilateral facial palsy (40%), impaired hearing, and/or swallowing problems (70%-90%). Abnormal outer ears, ossicular malformations, Mondini defect of the cochlea and absent or hypoplastic semicircular canals (>90%). Cryptorchidism in males and hypogonadotropic hypogonadism in both males and females. Developmental delay. Cardiovascular malformations (75%-85%). Growth deficiency (70%-80%). Orofacial clefts (15%-20%). Tracheoesophageal fistula (15%-20%). Neonates with CHARGE syndrome often have multiple life-threatening medical conditions. Feeding difficulties are a major cause of morbidity in all age groups.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 16, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 10
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 8:60741739

- History of neurodevelopmental disorder

  ### History of neurodevelopmental disorder

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 16, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 10
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 8:60741739

- Hypogonadism with anosmia

  ### Hypogonadism with anosmia

  Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) is characterized by inappropriately low serum concentrations of the gonadotropins LH (luteinizing hormone) and FSH (follicle-stimulating hormone) in the presence of low circulating concentrations of sex steroids. IGD is associated with a normal sense of smell (normosmic IGD) in approximately 40% of affected individuals and an impaired sense of smell (Kallmann syndrome) in approximately 60%. IGD can first become apparent in infancy, adolescence, or adulthood. Infant boys with congenital IGD often have micropenis and cryptorchidism. Adolescents and adults with IGD have clinical evidence of hypogonadism and incomplete sexual maturation on physical examination. Adult males with IGD tend to have prepubertal testicular volume (i.e., <4 mL), absence of secondary sexual features (e.g., facial and axillary hair growth, deepening of the voice), decreased muscle mass, diminished libido, erectile dysfunction, and infertility. Adult females have little or no breast development and primary amenorrhea. Although skeletal maturation is delayed, the rate of linear growth is usually normal except for the absence of a distinct pubertal growth spurt.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 16, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 10
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 8:60741739

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 16, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 10
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 8:60741739

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 16, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 10
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 8:60741739

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (5)

Hetero

TA

Gene: DEPDC5
Variant: c.2481G>A
(p.Pro827=)
rsID: rs61731664
Ref Allele: G
Alt Allele: A
Freq: 1.3491%uncommon
CADD: 0.027

ClinVar Submissions (4)

- Epilepsy, familial focal, with variable foci 1, Autosomal dominant

  ### Epilepsy, familial focal, with variable foci 1

  DEPDC5-related epilepsy encompasses a range of epilepsy syndromes, almost all of which are characterized by focal seizures, with seizure onset in a discrete area of the brain. While most individuals with DEPDC5-related epilepsy have a normal brain MRI, some have epilepsy associated with a cortical malformation, usually focal cortical dysplasia. Seizure syndromes include familial focal epilepsy with variable foci (FFEVF), autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), familial mesial temporal lobe epilepsies (FMTLE), autosomal dominant epilepsy with auditory features (ADEAF), and infantile spasms. Although psychomotor development is usually normal, intellectual disability or autism spectrum disorder has been reported in some individuals.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 07, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 22:31838811

- Seizures

  ### Seizures

  Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or "seizure disorder."

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 07, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 22:31838811

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 07, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 22:31838811

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 07, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 22:31838811

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: DEPDC5
Variant: c.2055C>A
(p.Phe685Leu)
rsID: rs61731667
Ref Allele: C
Alt Allele: A
Freq: 1.3602%uncommon
CADD: 17.61

ClinVar Submissions (4)

- Epilepsy, familial focal, with variable foci 1, Autosomal dominant

  ### Epilepsy, familial focal, with variable foci 1

  DEPDC5-related epilepsy encompasses a range of epilepsy syndromes, almost all of which are characterized by focal seizures, with seizure onset in a discrete area of the brain. While most individuals with DEPDC5-related epilepsy have a normal brain MRI, some have epilepsy associated with a cortical malformation, usually focal cortical dysplasia. Seizure syndromes include familial focal epilepsy with variable foci (FFEVF), autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), familial mesial temporal lobe epilepsies (FMTLE), autosomal dominant epilepsy with auditory features (ADEAF), and infantile spasms. Although psychomotor development is usually normal, intellectual disability or autism spectrum disorder has been reported in some individuals.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 07, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 22:31822741

- Seizures

  ### Seizures

  Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or "seizure disorder."

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 07, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 22:31822741

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 07, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 22:31822741

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 07, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 22:31822741

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

CA

Gene: ETFDH
Variant: c.1690+15C>T
rsID: rs11931339
Ref Allele: C
Alt Allele: T
Freq: 1.3682%uncommon
CADD: 0.952

ClinVar Submissions (2)

- Glutaric aciduria, type 2, Autosomal recessive

  ### Glutaric aciduria, type 2

  Glutaric aciduria II (GA2) is an autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It differs from GA I (GA1; 231670) in that multiple acyl-CoA dehydrogenase deficiencies result in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids. GA II results from deficiency of any 1 of 3 molecules: the alpha (ETFA) and beta (ETFB) subunits of electron transfer flavoprotein, and electron transfer flavoprotein dehydrogenase (ETFDH). The clinical picture of GA II due to the different defects appears to be indistinguishable; each defect can lead to a range of mild or severe cases, depending presumably on the location and nature of the intragenic lesion, i.e., mutation, in each case (Goodman, 1993; Olsen et al., 2003). The heterogeneous clinical features of patients with MADD fall into 3 classes: a neonatal-onset form with congenital anomalies (type I), a neonatal-onset form without congenital anomalies (type II), and a late-onset form (type III). The neonatal-onset forms are usually fatal and are characterized by severe nonketotic hypoglycemia, metabolic acidosis, multisystem involvement, and excretion of large amounts of fatty acid- and amino acid-derived metabolites. Symptoms and age at presentation of late-onset MADD are highly variable and characterized by recurrent episodes of lethargy, vomiting, hypoglycemia, metabolic acidosis, and hepatomegaly often preceded by metabolic stress. Muscle involvement in the form of pain, weakness, and lipid storage myopathy also occurs. The organic aciduria in patients with the late-onset form of MADD is often intermittent and only evident during periods of illness or catabolic stress (summary by Frerman and Goodman, 2001). Importantly, riboflavin treatment has been shown to ameliorate the symptoms and metabolic profiles in many MADD patients, particularly those with type III, the late-onset and mildest form (Liang et al., 2009).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 4:158706865

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 4:158706865

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CT

Gene: ANO5
Variant: c.*2095G>A
rsID: rs142192440
Ref Allele: G
Alt Allele: A
Freq: 1.3722%uncommon
CADD: 3.953

ClinVar Submissions (1)

- Limb-Girdle Muscular Dystrophy, Recessive

  ### Limb-Girdle Muscular Dystrophy, Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 11:22281860

- Miyoshi myopathy

  ### Miyoshi myopathy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 11:22281860

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: DEPDC5
Variant: c.4512C>T
(p.His1504=)
rsID: rs146449468
Ref Allele: C
Alt Allele: T
Freq: 1.3969%uncommon
CADD: 9.249

ClinVar Submissions (4)

- Epilepsy, familial focal, with variable foci 1, Autosomal dominant

  ### Epilepsy, familial focal, with variable foci 1

  DEPDC5-related epilepsy encompasses a range of epilepsy syndromes, almost all of which are characterized by focal seizures, with seizure onset in a discrete area of the brain. While most individuals with DEPDC5-related epilepsy have a normal brain MRI, some have epilepsy associated with a cortical malformation, usually focal cortical dysplasia. Seizure syndromes include familial focal epilepsy with variable foci (FFEVF), autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), familial mesial temporal lobe epilepsies (FMTLE), autosomal dominant epilepsy with auditory features (ADEAF), and infantile spasms. Although psychomotor development is usually normal, intellectual disability or autism spectrum disorder has been reported in some individuals.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 07, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 22:31906059

- Seizures

  ### Seizures

  Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or "seizure disorder."

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 07, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 22:31906059

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 07, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 22:31906059

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 07, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 22:31906059

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: ITGA7
Variant: c.1965T>C
(p.Cys655=)
rsID: rs7971022
Ref Allele: A
Alt Allele: G
Freq: 1.3992%uncommon
CADD: 5.582

ClinVar Submissions (6)

- Congenital Muscular Dystrophy, ITGA7-related

  ### Congenital Muscular Dystrophy, ITGA7-related

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 11, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 6
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 12:55695560

- Muscular dystrophy, congenital, due to integrin alpha-7 deficiency, Autosomal recessive

  ### Muscular dystrophy, congenital, due to integrin alpha-7 deficiency

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 11, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 6
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 12:55695560

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 11, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 6
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 12:55695560

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (2)

Hetero

AG

Gene: RYR2
Variant: c.4684-5G>C
rsID: rs7522981
Ref Allele: G
Alt Allele: C
Freq: 1.4024%uncommon
CADD: 0.61

ClinVar Submissions (4)

- Arrhythmogenic right ventricular cardiomyopathy

  ### Arrhythmogenic right ventricular cardiomyopathy

  Arrhythmogenic right ventricular cardiomyopathy (ARVC) – previously referred to as arrhythmogenic right ventricular dysplasia (ARVD) – is characterized by progressive fibrofatty replacement of the myocardium that predisposes to ventricular tachycardia and sudden death in young individuals and athletes. It primarily affects the right ventricle, and it may also involve the left ventricle. The presentation of disease is highly variable even within families, and some affected individuals may not meet established clinical criteria. The mean age at diagnosis is 31 years (±13; range: 4-64 years).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 22, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:237610757

- Cardiovascular phenotype

  ### Cardiovascular phenotype

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 22, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:237610757

- Catecholaminergic polymorphic ventricular tachycardia, Autosomal dominant

  ### Catecholaminergic polymorphic ventricular tachycardia

  Catecholaminergic polymorphic ventricular tachycardia (CPVT) is characterized by episodic syncope occurring during exercise or acute emotion in individuals without structural cardiac abnormalities. The underlying cause of these episodes is the onset of fast ventricular tachycardia (bidirectional or polymorphic). Spontaneous recovery may occur when these arrhythmias self-terminate. In other instances, ventricular tachycardia may degenerate into ventricular fibrillation and cause sudden death if cardiopulmonary resuscitation is not readily available. The mean age of onset of symptoms (usually a syncopal episode) is between age seven and twelve years; onset as late as the fourth decade of life has been reported. If untreated, CPVT is highly lethal, as approximately 30% of affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. Sudden death may be the first manifestation of the disease.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 22, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:237610757

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 22, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:237610757

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

GC

Gene: SOS2
Variant: c.816T>C
(p.Ser272=)
rsID: rs35396088
Ref Allele: A
Alt Allele: G
Freq: 1.4104%uncommon
CADD: 10.21

ClinVar Submissions (3)

- Noonan syndrome 9, Autosomal dominant

  ### Noonan syndrome 9

  Noonan syndrome is an autosomal dominant disorder characterized by short stature, craniofacial dysmorphism, short and/or webbed neck, cardiac abnormalities, cryptorchidism, and coagulation defects (summary by Yamamoto et al., 2015). For a phenotypic description and a discussion of genetic heterogeneity of Noonan syndrome, see NS1 (163950).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 09, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 14:50182505

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 09, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 14:50182505

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 09, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 14:50182505

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

AG

Gene: MSH2
Variant: c.1386+104C>T
rsID: rs17224444
Ref Allele: C
Alt Allele: T
Freq: 1.4271%uncommon
CADD: 0.044

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 2:47445761

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CT

Gene: BLK
Variant: c.211G>A
(p.Ala71Thr)
rsID: rs55758736
Ref Allele: G
Alt Allele: A
Freq: 1.4478%uncommon
CADD: 11.98

ClinVar Submissions (7)

- Maturity onset diabetes mellitus in young, Autosomal dominant

  ### Maturity onset diabetes mellitus in young

  Maturity-onset diabetes of the young is an autosomal dominant form of diabetes typically occurring before 25 years of age and caused by primary insulin secretion defects. Despite its low prevalence, MODY is not a single entity but represents genetic, metabolic, and clinical heterogeneity (Vaxillaire and Froguel, 2008). Genetic Heterogeneity of MODY MODY1 (125850) is caused by heterozygous mutation in the hepatocyte nuclear factor-4-alpha gene (HNF4A; 600281) on chromosome 20. MODY2 (125851) is caused by heterozygous mutation in the glucokinase gene (GCK; 138079) on chromosome 7. MODY3 (600496) is caused by heterozygous mutation in the hepatocyte nuclear factor-1alpha gene (HNF1A; 142410) on chromosome 12q24.2. MODY4 (606392) is caused by heterozygous mutation in the pancreas/duodenum homeobox protein-1 gene (PDX1; 600733) on chromosome 13q12.1. MODY5 (137920) is caused by heterozygous mutation in the gene encoding hepatic transcription factor-2 (TCF2; 189907) on chromosome 17cen-q21.3. MODY6 (606394) is caused by heterozygous mutation in the NEUROD1 gene (601724) on chromosome 2q32. MODY7 (610508) is caused by heterozygous mutation in the KLF11 gene (603301) on chromosome 2p25. MODY8 (609812), or diabetes-pancreatic exocrine dysfunction syndrome, is caused by heterozygous mutation in the CEL gene (114840) on chromosome 9q34. MODY9 (612225) is caused by heterozygous mutation in the PAX4 gene (167413) on chromosome 7q32. MODY10 (613370) is caused by heterozygous mutation in the insulin gene (INS; 176730) on chromosome 11p15.5. MODY11 (613375) is caused by heterozygous mutation in the BLK gene (191305) on chromosome 8p23. MODY13 (616329) is caused by heterozygous mutation in the KCNJ11 gene (600937) on chromosome 11p15. MODY14 (616511) is caused by heterozygous mutation in the APPL1 gene (604299) on chromosome 3p14.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 21, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 7
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 8:11548067
  OMIM Allelic Variant: 191305.0001

- Maturity-onset diabetes of the young, type 11, Autosomal dominant

  ### Maturity-onset diabetes of the young, type 11

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 21, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 7
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 8:11548067
  OMIM Allelic Variant: 191305.0001

- Monogenic diabetes

  ### Monogenic diabetes

  Diabetes mellitus caused by mutation(s) in a single gene, usually presenting in childhood or early adulthood.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 21, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 7
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 8:11548067
  OMIM Allelic Variant: 191305.0001

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 21, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 7
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 8:11548067
  OMIM Allelic Variant: 191305.0001

Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (7)

Hetero

GA

Gene: TFAP2B
Variant: c.*3074C>T
rsID: rs147683287
Ref Allele: C
Alt Allele: T
Freq: 1.4534%uncommon
CADD: 0.309

ClinVar Submissions (1)

- Char syndrome, Autosomal dominant

  ### Char syndrome

  Char syndrome is characterized by the triad of typical facial features, patent ductus arteriosus (PDA), and aplasia or hypoplasia of the middle phalanges of the fifth fingers. Typical facial features are flat midface, flat nasal bridge and broad flat nasal tip, wide-set eyes, downslanting palpebral fissures, mild ptosis, short philtrum resulting in a triangular mouth, and thickened (patulous) everted lips.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 6:50846466

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CT

Gene: PCBD1
Variant: c.*253T>A
rsID: rs77029400
Ref Allele: A
Alt Allele: T
Freq: 1.4614%uncommon
CADD: 9.894

ClinVar Submissions (1)

- BH4-Deficient Hyperphenylalaninemia

  ### BH4-Deficient Hyperphenylalaninemia

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 10:70883697

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

AT

Gene: CNGB1
Variant: c.*281T>C
rsID: rs116564376
Ref Allele: A
Alt Allele: G
Freq: 1.4653%uncommon
CADD: 2.336

ClinVar Submissions (1)

- Retinitis Pigmentosa, Recessive

  ### Retinitis Pigmentosa, Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 16:57883883

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

AG

Gene: SLC26A2
Variant: c.1474C>T
(p.Arg492Trp)
rsID: rs78676079
Ref Allele: C
Alt Allele: T
Freq: 1.4749%uncommon
CADD: 24

ClinVar Submissions (7)

- Achondrogenesis

  ### Achondrogenesis

  A rare group of disorders characterized by defective development of bones and cartilage.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 01, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:149981067

- Achondrogenesis, type IB, Autosomal recessive

  ### Achondrogenesis, type IB

  Clinical features of achondrogenesis type 1B (ACG1B) include extremely short limbs with short fingers and toes, hypoplasia of the thorax, protuberant abdomen, and hydropic fetal appearance caused by the abundance of soft tissue relative to the short skeleton. The face is flat, the neck is short, and the soft tissue of the neck may be thickened. Death occurs prenatally or shortly after birth.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 01, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:149981067

- Atelosteogenesis

  ### Atelosteogenesis

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 01, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:149981067

- Atelosteogenesis type 2, Autosomal recessive

  ### Atelosteogenesis type 2

  Clinical features of atelosteogenesis type 2 (AO2) include rhizomelic limb shortening with normal-sized skull, hitchhiker thumbs, small chest, protuberant abdomen, cleft palate, and distinctive facial features (midfaceretrusion, depressed nasal bridge, epicanthus, micrognathia). Other typical findings are ulnar deviation of the fingers, gap between the first and second toes, and clubfoot. AO2 is lethal at birth or shortly thereafter because of pulmonary hypoplasia and tracheobronchomalacia.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 01, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:149981067

- Diastrophic dysplasia, Autosomal recessive

  ### Diastrophic dysplasia

  Diastrophic dysplasia (DTD) is characterized by limb shortening, normal-sized skull, hitchhiker thumbs, spinal deformities (scoliosis, exaggerated lumbar lordosis, cervical kyphosis), and contractures of the large joints with deformities and early-onset osteoarthritis. Other typical findings are ulnar deviation of the fingers, gap between the first and second toes, and clubfoot. On occasion the disease can be lethal at birth, but most affected individuals survive the neonatal period and develop physical limitations with normal intelligence.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 01, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:149981067

- Diastrophic dysplasia, Autosomal recessive

  ### Diastrophic dysplasia

  Diastrophic dysplasia (DTD) is characterized by limb shortening, normal-sized skull, hitchhiker thumbs, spinal deformities (scoliosis, exaggerated lumbar lordosis, cervical kyphosis), and contractures of the large joints with deformities and early-onset osteoarthritis. Other typical findings are ulnar deviation of the fingers, gap between the first and second toes, and clubfoot. On occasion the disease can be lethal at birth, but most affected individuals survive the neonatal period and develop physical limitations with normal intelligence.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 01, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:149981067

- Multiple epiphyseal dysplasia 4, Autosomal recessive

  ### Multiple epiphyseal dysplasia 4

  Recessive multiple epiphyseal dysplasia (EDM4/rMED) is characterized by joint pain (usually in the hips or knees); malformations of hands, feet, and knees; and scoliosis. Approximately 50% of affected individuals have an abnormal finding at birth, e.g., clubfoot, clinodactyly, or (rarely) cystic ear swelling. Onset of articular pain is variable but usually occurs in late childhood. Stature is usually within the normal range prior to puberty; in adulthood, stature is only slightly diminished and ranges from 150 to 180 cm. Functional disability is mild.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 01, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:149981067

- Multiple epiphyseal dysplasia 4, Autosomal recessive

  ### Multiple epiphyseal dysplasia 4

  Recessive multiple epiphyseal dysplasia (EDM4/rMED) is characterized by joint pain (usually in the hips or knees); malformations of hands, feet, and knees; and scoliosis. Approximately 50% of affected individuals have an abnormal finding at birth, e.g., clubfoot, clinodactyly, or (rarely) cystic ear swelling. Onset of articular pain is variable but usually occurs in late childhood. Stature is usually within the normal range prior to puberty; in adulthood, stature is only slightly diminished and ranges from 150 to 180 cm. Functional disability is mild.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 01, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:149981067

- Osteochondrodysplasia

  ### Osteochondrodysplasia

  A general term describing features characterized by abnormal development of bones and connective tissues. [HPO:probinson]

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 01, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:149981067

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 01, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:149981067

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 01, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:149981067

Insufficiently evaluated pathogenic — This variant was found in "numerous" autosomal recessive diastrophic dysplasia patients, but later evidence point to it likely being a benign polymorphism.

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (6)

Hetero

CT

Gene: KRT12
Variant: c.*360A>C
rsID: rs62065925
Ref Allele: T
Alt Allele: G
Freq: 1.4932%uncommon
CADD: 3.446

ClinVar Submissions (1)

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: no assertion provided
  Number of Submitters: 1
  Clinical Significance: not provided
  Assembly: GRCh38
  Chromosome/Position: 17:40861301

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

TG

Gene: TRIP11
Variant: c.4727G>A
(p.Arg1576His)
rsID: rs35007347
Ref Allele: C
Alt Allele: T
Freq: 1.5155%uncommon
CADD: 23.7

ClinVar Submissions (2)

- Achondrogenesis

  ### Achondrogenesis

  A rare group of disorders characterized by defective development of bones and cartilage.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 04, 2016
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 2
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 14:91999405

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 04, 2016
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 2
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 14:91999405

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OpenSNP
- PubMed

Hetero

CT

Gene: KCNJ1
Variant: c.*597C>T
rsID: rs117189807
Ref Allele: G
Alt Allele: A
Freq: 1.5179%uncommon
CADD: 0.165

ClinVar Submissions (1)

- Antenatal Bartter Syndrome

  ### Antenatal Bartter Syndrome

  Bartter syndrome is a group of very similar kidney disorders that cause an imbalance of potassium, sodium, chloride, and related molecules in the body.In some cases, Bartter syndrome becomes apparent before birth. The disorder can cause polyhydramnios, which is an increased volume of fluid surrounding the fetus (amniotic fluid). Polyhydramnios increases the risk of premature birth.Beginning in infancy, affected individuals often fail to grow and gain weight at the expected rate (failure to thrive). They lose excess amounts of salt (sodium chloride) in their urine, which leads to dehydration, constipation, and increased urine production (polyuria). In addition, large amounts of calcium are lost through the urine (hypercalciuria), which can cause weakening of the bones (osteopenia). Some of the calcium is deposited in the kidneys as they are concentrating urine, leading to hardening of the kidney tissue (nephrocalcinosis). Bartter syndrome is also characterized by low levels of potassium in the blood (hypokalemia), which can result in muscle weakness, cramping, and fatigue. Rarely, affected children develop hearing loss caused by abnormalities in the inner ear (sensorineural deafness).Two major forms of Bartter syndrome are distinguished by their age of onset and severity. One form begins before birth (antenatal) and is often life-threatening. The other form, often called the classical form, begins in early childhood and tends to be less severe. Once the genetic causes of Bartter syndrome were identified, researchers also split the disorder into different types based on the genes involved. Types I, II, and IV have the features of antenatal Bartter syndrome. Because type IV is also associated with hearing loss, it is sometimes called antenatal Bartter syndrome with sensorineural deafness. Type III usually has the features of classical Bartter syndrome.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 11:128838528

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: UNC13D
Variant: c.175G>A
(p.Ala59Thr)
rsID: rs9904366
Ref Allele: C
Alt Allele: T
Freq: 1.5195%uncommon
CADD: 16.13

ClinVar Submissions (2)

- Hemophagocytic lymphohistiocytosis, familial, 3, Autosomal recessive

  ### Hemophagocytic lymphohistiocytosis, familial, 3

  Familial hemophagocytic lymphohistiocytosis (FHL) is characterized by proliferation and infiltration of hyperactivated macrophages and T-lymphocytes manifesting as acute illness with prolonged fever, cytopenias, and hepatosplenomegaly. Onset is typically within the first months or years of life and, on occasion, in utero, although later childhood or adult onset is more common than previously suspected. Neurologic abnormalities may be present initially or may develop later; they may include increased intracranial pressure, irritability, neck stiffness, hypotonia, hypertonia, convulsions, cranial nerve palsies, ataxia, hemiplegia, quadriplegia, blindness, and coma. Rash and lymphadenopathy are less common. Other findings include liver dysfunction and bone marrow hemophagocytosis. The median survival of children with typical FHL, without treatment, is less than two months; progression of hemophagocytic lymphohistiocytosis and infection account for the majority of deaths in untreated individuals.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 31, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 17:75843245

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 31, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 17:75843245

Low clinical importance, Uncertain benign — Probably benign. This variant was reported to cause haemophagocytic lymphohistiocytosis in a recessive manner, but its allele frequency is inconsistent with this hypothesis and so we evaluate it as a nonpathogenic polymorphism.

Benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: NIN
Variant: c.3459G>A
(p.Arg1153=)
rsID: rs41310342
Ref Allele: C
Alt Allele: T
Freq: 1.5203%uncommon
CADD: 0.406

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 14:50757571

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CT

Gene: RGS9BP
Variant: c.696G>A
(p.Ala232=)
rsID: rs150936907
Ref Allele: G
Alt Allele: A
Freq: 1.5299%uncommon
CADD: 15.18

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 17, 2014
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 19:32676959

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: SETX
Variant: c.*849G>T
rsID: rs74975459
Ref Allele: C
Alt Allele: A
Freq: 1.5354%uncommon
CADD: 1.358

ClinVar Submissions (1)

- Amyotrophic Lateral Sclerosis, Dominant

  ### Amyotrophic Lateral Sclerosis, Dominant

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 9:132263390

- Ataxia with Oculomotor Apraxia

  ### Ataxia with Oculomotor Apraxia

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 9:132263390

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Homo

AA

Gene: GSDME
Variant: c.1199C>T
(p.Ala400Val)
rsID: rs71535705
Ref Allele: G
Alt Allele: A
Freq: 1.541%uncommon
CADD: 16.32

ClinVar Submissions (2)

- Nonsyndromic Hearing Loss, Mixed

  ### Nonsyndromic Hearing Loss, Mixed

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 7:24702818

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 7:24702818

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: INF2
Variant: c.391+17G>A
rsID: rs4074531
Ref Allele: G
Alt Allele: A
Freq: 1.541%uncommon
CADD: 0.756

ClinVar Submissions (3)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 06, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 14:104701773

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: RBFOX1
Variant: c.1134+3G>A
rsID: rs79369633
Ref Allele: G
Alt Allele: A
Freq: 1.5482%uncommon
CADD: 14.5

ClinVar Submissions (2)

- Idiopathic generalized epilepsy, Autosomal dominant

  ### Idiopathic generalized epilepsy

  Idiopathic generalized epilepsy is a broad term that encompasses several common seizure phenotypes, classically including childhood absence epilepsy (CAE, ECA; see 600131), juvenile absence epilepsy (JAE, EJA; see 607631), juvenile myoclonic epilepsy (JME, EJM; see 254770), and epilepsy with grand mal seizures on awakening (Commission on Classification and Terminology of the International League Against Epilepsy, 1989). These recurrent seizures occur in the absence of detectable brain lesions and/or metabolic abnormalities. Seizures are initially generalized with a bilateral, synchronous, generalized, symmetrical EEG discharge (Zara et al., 1995; Lu and Wang, 2009). See also childhood absence epilepsy (ECA1; 600131), which has also been mapped to 8q24. Of note, benign neonatal epilepsy 2 (EBN2; 121201) is caused by mutation in the KCNQ3 gene (602232) on 8q24. Genetic Heterogeneity of Idiopathic Generalized Epilepsy EIG1 has been mapped to chromosome 8q24. Other loci or genes associated with EIG include EIG2 (606972) on 14q23; EIG3 (608762) on 9q32; EIG4 (609750) on 10q25; EIG5 (611934) on 10p11; EIG6 (611942), caused by mutation in the CACNA1H gene (607904) on 16p; EIG7 (604827) on 15q14; EIG8 (612899), caused by mutation in the CASR gene (601199) on 3q13.3-q21; EIG9 (607682), caused by mutation in the CACNB4 gene (601949) on 2q22-q23; EIG10 (613060), caused by mutation in the GABRD gene (137163) on 1p36.3; EIG11 (607628), caused by variation in the CLCN2 gene (600570) on 3q36; EIG12 (614847), caused by mutation in the SLC2A1 gene (138140) on 1p34; EIG13 (611136), caused by mutation in the GABRA1 gene (137160) on 5q34; EIG14 (616685), caused by mutation in the SLC12A5 gene (606726) on 20q12; and EIG15 (618357), caused by mutation in the RORB gene (601972) on 9q22.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 03, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 16:7709134

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 03, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 16:7709134

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GA

Gene: BANF1
Variant: c.*177G>A
rsID: rs148797275
Ref Allele: G
Alt Allele: A
Freq: 1.5553%uncommon
CADD: 3.246

ClinVar Submissions (1)

- Nestor-Guillermo progeria syndrome, Autosomal recessive

  ### Nestor-Guillermo progeria syndrome

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 11:66003949

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GA

Gene: AKR1D1
Variant: c.*58G>C
rsID: rs80147006
Ref Allele: G
Alt Allele: C
Freq: 1.58%uncommon
CADD: 1.1

ClinVar Submissions (1)

- Congenital Bile Acid Synthesis Defect

  ### Congenital Bile Acid Synthesis Defect

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 7:138116720

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GC

Gene: SCNN1G
Variant: c.636C>T
(p.Ser212=)
rsID: rs5739
Ref Allele: C
Alt Allele: T
Freq: 1.596%uncommon
CADD: 0.274

ClinVar Submissions (3)

- Pseudohypoaldosteronism type 1 autosomal recessive, Autosomal recessive

  ### Pseudohypoaldosteronism type 1 autosomal recessive

  Autosomal recessive pseudohypoaldosteronism type I is characterized by renal salt wasting and high concentrations of sodium in sweat, stool, and saliva. The disorder involves multiple organ systems and is especially threatening in the neonatal period. Laboratory evaluation shows hyponatremia, hyperkalemia, and increased plasma renin activity with high serum aldosterone concentrations. Respiratory tract infections are common in affected children and may be mistaken for cystic fibrosis (CF; 219700). Aggressive salt replacement and control of hyperkalemia results in survival, and the disorder appears to become less severe with age (review by Scheinman et al., 1999). A milder, autosomal dominant form of type I pseudohypoaldosteronism (PHA1A; 177735) is caused by mutations in the mineralocorticoid receptor gene (MCR, NR3C2; 600983). Gitelman syndrome (263800), another example of primary renal tubular salt wasting, is due to mutation in the thiazide-sensitive sodium-chloride cotransporter (SLC12A3; 600968). Hanukoglu and Hanukoglu (2016) provided a detailed review of the ENaC gene family, including structure, function, tissue distribution, and associated inherited diseases.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 16, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 16:23192369

- Pseudoprimary hyperaldosteronism, Autosomal dominant

  ### Pseudoprimary hyperaldosteronism

  Liddle syndrome is an autosomal dominant disorder characterized by early-onset salt-sensitive hypertension, hypokalemia, metabolic alkalosis, and suppression of plasma renin activity and aldosterone secretion (summary by Yang et al., 2014). Genetic Heterogeneity of Liddle Syndrome Liddle syndrome-2 (618114) is caused by mutation in the SCNN1G gene (600761), which encodes the ENaC gamma subunit. Liddle syndrome-3 (618126) is caused by mutation in the SCNN1A gene (600228), which encodes the ENaC alpha subunit. Hanukoglu and Hanukoglu (2016) provided a detailed review of the ENaC gene family, including structure, function, tissue distribution, and associated inherited diseases.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 16, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 16:23192369

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 16, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 16:23192369

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 16, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 16:23192369

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: NSD1
Variant: c.2071G>A
(p.Ala691Thr)
rsID: rs28932177
Ref Allele: G
Alt Allele: A
Freq: 1.6318%uncommon
CADD: 14.23

ClinVar Submissions (6)

- Beckwith-Wiedemann syndrome, Autosomal dominant

  ### Beckwith-Wiedemann syndrome

  Beckwith-Wiedemann syndrome (BWS) is a growth disorder variably characterized by neonatal hypoglycemia, macrosomia, macroglossia, hemihyperplasia, omphalocele, embryonal tumors (e.g., Wilms tumor, hepatoblastoma, neuroblastoma, and rhabdomyosarcoma), visceromegaly, adrenocortical cytomegaly, renal abnormalities (e.g., medullary dysplasia, nephrocalcinosis, medullary sponge kidney, and nephromegaly), and ear creases/pits. BWS is considered a clinical spectrum, in which affected individuals may have many of these features or may have only one or two clinical features. Early death may occur from complications of prematurity, hypoglycemia, cardiomyopathy, macroglossia, or tumors. However, the previously reported mortality of 20% is likely an overestimate given better recognition of the disorder along with enhanced treatment options. Macroglossia and macrosomia are generally present at birth but may have postnatal onset. Growth rate slows around age seven to eight years. Hemihyperplasia may affect segmental regions of the body or selected organs and tissues.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 26, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:177210470

- History of neurodevelopmental disorder

  ### History of neurodevelopmental disorder

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 26, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:177210470

- Sotos syndrome

  ### Sotos syndrome

  Sotos syndrome is a disorder characterized by a distinctive facial appearance, overgrowth in childhood, and learning disabilities or delayed development of mental and movement abilities. Characteristic facial features include a long, narrow face; a high forehead; flushed (reddened) cheeks; and a small, pointed chin. In addition, the outside corners of the eyes may point downward (down-slanting palpebral fissures). This facial appearance is most notable in early childhood. Affected infants and children tend to grow quickly; they are significantly taller than their siblings and peers and have an unusually large head. However, adult height is usually in the normal range.People with Sotos syndrome often have intellectual disability, and most also have behavioral problems. Frequent behavioral issues include attention deficit hyperactivity disorder (ADHD), phobias, obsessions and compulsions, tantrums, and impulsive behaviors. Problems with speech and language are also common. Affected individuals often have a stutter, a monotone voice, and problems with sound production. Additionally, weak muscle tone (hypotonia) may delay other aspects of early development, particularly motor skills such as sitting and crawling.Other signs and symptoms of Sotos syndrome can include an abnormal side-to-side curvature of the spine (scoliosis), seizures, heart or kidney defects, hearing loss, and problems with vision. Some infants with this disorder experience yellowing of the skin and whites of the eyes (jaundice) and poor feeding.A small percentage of people with Sotos syndrome have developed cancer, most often in childhood, but no single form of cancer occurs most frequently with this condition. It remains uncertain whether Sotos syndrome increases the risk of specific types of cancer. If people with this disorder have an increased cancer risk, it is only slightly greater than that of the general population.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 26, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:177210470

- Weaver syndrome, Autosomal dominant

  ### Weaver syndrome

  EZH2-related overgrowth includes EZH2-related Weaver syndrome at one end of the spectrum and tall stature at the other. Although most individuals diagnosed with a heterozygous EZH2 pathogenic variant have been identified because of a clinical suspicion of Weaver syndrome, a minority have been identified through molecular genetic testing of family members of probands or individuals with overgrowth who did not have a clinical diagnosis of Weaver syndrome. Thus, the extent of the phenotypic spectrum associated with a heterozygous EZH2 pathogenic variant is not yet known. Weaver syndrome is characterized by tall stature, variable intellect (ranging from normal intellect to severe intellectual disability), characteristic facial appearance, and a range of associated clinical features including advanced bone age, poor coordination, soft doughy skin, camptodactyly of the fingers and/or toes, umbilical hernia, abnormal tone, and hoarse low cry in infancy. Brain MRI has identified abnormalities in a few individuals with EZH2-related overgrowth. Neuroblastoma occurs at a slightly increased frequency in individuals with a heterozygous EZH2 pathogenic variant but data are insufficient to determine absolute risk. There is currently no evidence that additional malignancies (including hematologic malignancies) occur with increased frequency.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 26, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:177210470

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 26, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:177210470

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (3)

Hetero

GA

Gene: NSD1
Variant: c.927+48A>G
rsID: rs79928962
Ref Allele: A
Alt Allele: G
Freq: 1.6342%uncommon
CADD: 16.58

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 5:177136078

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

AG

Gene: FBLN5
Variant: c.1122C>T
(p.Tyr374=)
rsID: rs145515678
Ref Allele: G
Alt Allele: A
Freq: 1.6358%uncommon
CADD: 18.81

ClinVar Submissions (2)

- Cutis Laxa, Dominant/Recessive

  ### Cutis Laxa, Dominant/Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 25, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 14:91877550

- Macular degeneration

  ### Macular degeneration

  A nonspecific term denoting degeneration of the retinal pigment epithelium and/or retinal photoreceptor cells of the macula lutea.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 25, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 14:91877550

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 25, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 14:91877550

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: ACVRL1
Variant: c.*58G>A
rsID: rs182368657
Ref Allele: G
Alt Allele: A
Freq: 1.6374%uncommon
CADD: 2.63

ClinVar Submissions (2)

- Osler hemorrhagic telangiectasia syndrome, Autosomal dominant

  ### Osler hemorrhagic telangiectasia syndrome

  Hereditary hemorrhagic telangiectasia (HHT) is characterized by the presence of multiple arteriovenous malformations (AVMs) that lack intervening capillaries and result in direct connections between arteries and veins. The most common clinical manifestation is spontaneous and recurrent nosebleeds (epistaxis) beginning on average at age 12 years. Telangiectases (small AVMs) are most evident on the lips, tongue, buccal mucosa, face, chest, and fingers. The average age of onset is generally later than epistaxis, but may be during childhood. Large AVMs often cause symptoms when they occur in the lungs, liver, or brain; complications from bleeding or shunting may be sudden and catastrophic. Approximately 25% of individuals with HHT have GI bleeding, which most commonly begins after age 50 years.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 02, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 12:51920951

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 02, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 12:51920951

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GA

Gene: PEX16
Variant: c.760G>C
(p.Val254Leu)
rsID: rs35214605
Ref Allele: C
Alt Allele: G
Freq: 1.6549%uncommon
CADD: 15.88

ClinVar Submissions (3)

- Peroxisome biogenesis disorders, Zellweger syndrome spectrum

  ### Peroxisome biogenesis disorders, Zellweger syndrome spectrum

  Zellweger spectrum disorder (ZSD) is a phenotypic continuum ranging from severe to mild. While individual phenotypes (e.g., Zellweger syndrome [ZS], neonatal adrenoleukodystrophy [NALD], and infantile Refsum disease [IRD]) were described in the past before the biochemical and molecular bases of this spectrum were fully determined, the term ZSD is now used to refer to all individuals with a PEX gene defect regardless of phenotype. Individuals with ZSD usually come to clinical attention in the newborn period or later in childhood. Affected newborns are hypotonic and feed poorly. They have distinctive facies, congenital malformations (neuronal migration defects associated with neonatal-onset seizures, renal cysts, and bony stippling [chondrodysplasia punctata] of the patella[e] and other long bones), and liver disease which can be severe. Infants with severe ZSD are significantly impaired and typically die during the first year of life, usually having made no developmental progress. Individuals with intermediate/milder ZSD do not have congenital malformations, but rather progressive peroxisome dysfunction variably manifest as sensory loss (secondary to retinal dystrophy and sensorineural hearing loss); neurologic involvement (ataxia, polyneuropathy, and leukodystrophy); liver dysfunction; adrenal insufficiency; and renal oxalate stones. While hypotonia and developmental delays are typical, intellect can be normal. Some have osteopenia; almost all have ameleogenesis imperfecta in the secondary teeth.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 03, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:45914138

- Zellweger syndrome, Autosomal recessive

  ### Zellweger syndrome

  Zellweger spectrum disorder (ZSD) is a phenotypic continuum ranging from severe to mild. While individual phenotypes (e.g., Zellweger syndrome [ZS], neonatal adrenoleukodystrophy [NALD], and infantile Refsum disease [IRD]) were described in the past before the biochemical and molecular bases of this spectrum were fully determined, the term ZSD is now used to refer to all individuals with a PEX gene defect regardless of phenotype. Individuals with ZSD usually come to clinical attention in the newborn period or later in childhood. Affected newborns are hypotonic and feed poorly. They have distinctive facies, congenital malformations (neuronal migration defects associated with neonatal-onset seizures, renal cysts, and bony stippling [chondrodysplasia punctata] of the patella[e] and other long bones), and liver disease which can be severe. Infants with severe ZSD are significantly impaired and typically die during the first year of life, usually having made no developmental progress. Individuals with intermediate/milder ZSD do not have congenital malformations, but rather progressive peroxisome dysfunction variably manifest as sensory loss (secondary to retinal dystrophy and sensorineural hearing loss); neurologic involvement (ataxia, polyneuropathy, and leukodystrophy); liver dysfunction; adrenal insufficiency; and renal oxalate stones. While hypotonia and developmental delays are typical, intellect can be normal. Some have osteopenia; almost all have ameleogenesis imperfecta in the secondary teeth.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 03, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:45914138

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 03, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:45914138

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed

Hetero

CG

Gene: CDH23
Variant: c.4207-18T>C
rsID: rs77770890
Ref Allele: T
Alt Allele: C
Freq: 1.6732%uncommon
CADD: 4.566

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 27, 2013
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 10:71734638

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

TC

Gene: STAT5B
Variant: c.1101C>A
(p.Pro367=)
rsID: rs61749920
Ref Allele: G
Alt Allele: T
Freq: 1.6899%uncommon
CADD: 4.677

ClinVar Submissions (3)

- Growth hormone insensitivity with immunodeficiency, Autosomal recessive

  ### Growth hormone insensitivity with immunodeficiency

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 31, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 17:42218219

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 31, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 17:42218219

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

GT

Gene: RUNX1
Variant: c.*1012C>T
rsID: rs55767668
Ref Allele: G
Alt Allele: A
Freq: 1.7051%uncommon
CADD: 7.776

ClinVar Submissions (1)

- Familial platelet disorder with associated myeloid malignancy, Autosomal dominant

  ### Familial platelet disorder with associated myeloid malignancy

  Disease that is characterised by moderate thrombocytopenia, abnormal platelet function and the propensity to develop myeloid malignancies, in particular acute myelogenous leukaemia. The prevalence is unknown but the disease has been reported in less than 20 families. Causative mutations have been identified in the RUNX1 gene (also known as AML1 or CBFA2; chromosome 21q22.3) in most of the analysed families. The condition is inherited as an autosomal dominant trait.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 21:34791123

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GA

Gene: NSD1
Variant: c.*4027T>C
rsID: rs114048132
Ref Allele: T
Alt Allele: C
Freq: 1.7202%uncommon
CADD: 15.78

ClinVar Submissions (1)

- Sotos syndrome

  ### Sotos syndrome

  Sotos syndrome is a disorder characterized by a distinctive facial appearance, overgrowth in childhood, and learning disabilities or delayed development of mental and movement abilities. Characteristic facial features include a long, narrow face; a high forehead; flushed (reddened) cheeks; and a small, pointed chin. In addition, the outside corners of the eyes may point downward (down-slanting palpebral fissures). This facial appearance is most notable in early childhood. Affected infants and children tend to grow quickly; they are significantly taller than their siblings and peers and have an unusually large head. However, adult height is usually in the normal range.People with Sotos syndrome often have intellectual disability, and most also have behavioral problems. Frequent behavioral issues include attention deficit hyperactivity disorder (ADHD), phobias, obsessions and compulsions, tantrums, and impulsive behaviors. Problems with speech and language are also common. Affected individuals often have a stutter, a monotone voice, and problems with sound production. Additionally, weak muscle tone (hypotonia) may delay other aspects of early development, particularly motor skills such as sitting and crawling.Other signs and symptoms of Sotos syndrome can include an abnormal side-to-side curvature of the spine (scoliosis), seizures, heart or kidney defects, hearing loss, and problems with vision. Some infants with this disorder experience yellowing of the skin and whites of the eyes (jaundice) and poor feeding.A small percentage of people with Sotos syndrome have developed cancer, most often in childhood, but no single form of cancer occurs most frequently with this condition. It remains uncertain whether Sotos syndrome increases the risk of specific types of cancer. If people with this disorder have an increased cancer risk, it is only slightly greater than that of the general population.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:177299486

- Weaver syndrome, Autosomal dominant

  ### Weaver syndrome

  EZH2-related overgrowth includes EZH2-related Weaver syndrome at one end of the spectrum and tall stature at the other. Although most individuals diagnosed with a heterozygous EZH2 pathogenic variant have been identified because of a clinical suspicion of Weaver syndrome, a minority have been identified through molecular genetic testing of family members of probands or individuals with overgrowth who did not have a clinical diagnosis of Weaver syndrome. Thus, the extent of the phenotypic spectrum associated with a heterozygous EZH2 pathogenic variant is not yet known. Weaver syndrome is characterized by tall stature, variable intellect (ranging from normal intellect to severe intellectual disability), characteristic facial appearance, and a range of associated clinical features including advanced bone age, poor coordination, soft doughy skin, camptodactyly of the fingers and/or toes, umbilical hernia, abnormal tone, and hoarse low cry in infancy. Brain MRI has identified abnormalities in a few individuals with EZH2-related overgrowth. Neuroblastoma occurs at a slightly increased frequency in individuals with a heterozygous EZH2 pathogenic variant but data are insufficient to determine absolute risk. There is currently no evidence that additional malignancies (including hematologic malignancies) occur with increased frequency.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:177299486

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

TC

Gene: SLC4A1
Variant: c.2712C>T
(p.Tyr904=)
rsID: rs45519733
Ref Allele: G
Alt Allele: A
Freq: 1.7321%uncommon
CADD: 0.024

ClinVar Submissions (2)

- Distal Renal Tubular Acidosis, Dominant

  ### Distal Renal Tubular Acidosis, Dominant

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 17:44250482

- Hemolytic anemia

  ### Hemolytic anemia

  A condition of inadequate circulating red blood cells (ANEMIA) or insufficient HEMOGLOBIN due to premature destruction of red blood cells (ERYTHROCYTES).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 17:44250482

- Spherocytosis, Dominant

  ### Spherocytosis, Dominant

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 17:44250482

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 17:44250482

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: GAN
Variant: c.*159C>T
rsID: rs76000455
Ref Allele: C
Alt Allele: T
Freq: 1.7353%uncommon
CADD: 10.56

ClinVar Submissions (1)

- Giant axonal neuropathy, Autosomal recessive

  ### Giant axonal neuropathy

  Giant axonal neuropathy (GAN) is an early-onset fatal neurodegenerative disorder. GAN starts as severe peripheral motor and sensory neuropathy during infancy and evolves into central nervous system impairment (intellectual disability, seizures, cerebellar signs, and pyramidal tract signs). Most individuals become wheelchair dependent in the second decade of life and eventually bedridden with severe polyneuropathy, ataxia, and dementia. Death usually occurs in the third decade.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 16:81377755

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CT

Gene: HGD
Variant: c.372C>T
(p.Asp124=)
rsID: rs140977117
Ref Allele: G
Alt Allele: A
Freq: 1.752%uncommon
CADD: 7.583

ClinVar Submissions (1)

- Alkaptonuria, Autosomal recessive

  ### Alkaptonuria

  Alkaptonuria is caused by deficiency of homogentisate 1,2-dioxygenase, an enzyme that converts homogentisic acid (HGA) to maleylacetoacetic acid in the tyrosine degradation pathway. The three major features of alkaptonuria are the presence of HGA in the urine, ochronosis (bluish-black pigmentation in connective tissue), and arthritis of the spine and larger joints. Oxidation of the HGA excreted in the urine produces a melanin-like product and causes the urine to turn dark on standing. Ochronosis occurs only after age 30 years; arthritis often begins in the third decade. Other manifestations include pigment deposition, aortic or mitral valve calcification or regurgitation and occasionally aortic dilatation, renal stones, and prostate stones.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 3:120650836

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GA

Gene: UNC13D
Variant: c.951+13T>G
rsID: rs140758914
Ref Allele: A
Alt Allele: C
Freq: 1.756%uncommon
CADD: 5.815

ClinVar Submissions (2)

- Familial hemophagocytic lymphohistiocytosis

  ### Familial hemophagocytic lymphohistiocytosis

  Familial hemophagocytic lymphohistiocytosis (FHL) is characterized by proliferation and infiltration of hyperactivated macrophages and T-lymphocytes manifesting as acute illness with prolonged fever, cytopenias, and hepatosplenomegaly. Onset is typically within the first months or years of life and, on occasion, in utero, although later childhood or adult onset is more common than previously suspected. Neurologic abnormalities may be present initially or may develop later; they may include increased intracranial pressure, irritability, neck stiffness, hypotonia, hypertonia, convulsions, cranial nerve palsies, ataxia, hemiplegia, quadriplegia, blindness, and coma. Rash and lymphadenopathy are less common. Other findings include liver dysfunction and bone marrow hemophagocytosis. The median survival of children with typical FHL, without treatment, is less than two months; progression of hemophagocytic lymphohistiocytosis and infection account for the majority of deaths in untreated individuals.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 2
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 17:75840005

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 2
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 17:75840005

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

AC

Gene: MTR
Variant: c.*5170A>G
rsID: rs6680753
Ref Allele: A
Alt Allele: G
Freq: 1.7712%uncommon
CADD: 1.515

ClinVar Submissions (1)

- Disorders of Intracellular Cobalamin Metabolism

  ### Disorders of Intracellular Cobalamin Metabolism

  Disorders of intracellular cobalamin metabolism have a variable phenotype and age of onset that are influenced by the severity and location within the pathway of the defect. The prototype and best understood phenotype is cblC; it is also the most common of these disorders. The age of initial presentation of cblC spans a wide range: In utero with fetal presentation of nonimmune hydrops, cardiomyopathy, and intrauterine growth restriction. Newborns, who can have microcephaly, poor feeding, and encephalopathy. Infants, who can have poor feeding and slow growth, neurologic abnormality, and, rarely, hemolytic uremic syndrome (HUS). Toddlers, who can have poor growth, progressive microcephaly, cytopenias (including megaloblastic anemia), global developmental delay, encephalopathy, and neurologic signs such as hypotonia and seizures. Adolescents and adults, who can have neuropsychiatric symptoms, progressive cognitive decline, thromboembolic compications, and/or subacute combined degeneration of the spinal cord.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:236902814

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

AG

Gene: DNAH8
Variant: c.11511G>A
(p.Arg3837=)
rsID: rs61748646
Ref Allele: G
Alt Allele: A
Freq: 1.8197%uncommon
CADD: 14.46

ClinVar Submissions (2)

- Ciliary dyskinesia

  ### Ciliary dyskinesia

  Primary ciliary dyskinesia (PCD) is associated with situs abnormalities, abnormal sperm motility, and abnormal ciliary structure and function that result in retention of mucus and bacteria in the respiratory tract leading to chronic otosinopulmonary disease. More than 75% of full-term neonates with PCD have "neonatal respiratory distress" requiring supplemental oxygen for days to weeks. Chronic airway infection, apparent in early childhood, results in bronchiectasis that is almost uniformly present in adulthood. Nasal congestion and sinus infections, apparent in early childhood, persist through adulthood. Chronic/recurrent ear infection, apparent in most young children, can be associated with transient or later irreversible hearing loss. Situs inversus totalis (mirror-image reversal of all visceral organs with no apparent physiologic consequences) is present in 40%-50% of individuals with PCD; heterotaxy (discordance of right and left patterns of ordinarily asymmetric structures that can be associated with significant malformations) is present in approximately 12%. Virtually all males with PCD are infertile as a result of abnormal sperm motility.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 27, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 6:38935645

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 27, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 6:38935645

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: TTN
Variant: c.35784G>A
(p.Arg11928=)
rsID: rs56034831
Ref Allele: C
Alt Allele: T
Freq: 1.8341%uncommon
CADD: 8.666

ClinVar Submissions (7)

- Cardiovascular phenotype

  ### Cardiovascular phenotype

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:178632406

- Dilated Cardiomyopathy, Dominant

  ### Dilated Cardiomyopathy, Dominant

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:178632406

- Dilated cardiomyopathy 1G, Autosomal dominant

  ### Dilated cardiomyopathy 1G

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:178632406

- Distal myopathy Markesbery-Griggs type, Autosomal dominant

  ### Distal myopathy Markesbery-Griggs type

  Udd distal myopathy is characterized by weakness of ankle dorsiflexion and inability to walk on the heels after age 35 years. Disease progression is slow and muscle weakness remains confined to the anterior tibial muscles. The long toe extensors become clinically involved after ten to 20 years, leading to foot drop and clumsiness when walking. In the mildest form, Udd distal myopathy can remain unnoticed even in the elderly.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:178632406

- Hereditary myopathy with early respiratory failure, Autosomal dominant

  ### Hereditary myopathy with early respiratory failure

  Hereditary myopathy with early respiratory failure (HMERF) is a slowly progressive myopathy that typically begins in the third to fifth decades of life. The usual presenting findings are gait disturbance relating to distal leg weakness or nocturnal respiratory symptoms due to respiratory muscle weakness. Weakness eventually generalizes and affects both proximal and distal muscles. Most affected individuals require walking aids within a few years of onset; some progress to wheelchair dependence and require nocturnal noninvasive ventilatory support. The disease course varies even among individuals within the same family: some remain ambulant until their 70s whereas others may require ventilator support in their 40s.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:178632406

- Hypertrophic cardiomyopathy

  ### Hypertrophic cardiomyopathy

  A condition in which the myocardium is hypertrophied without an obvious cause. The hypertrophy is generally asymmetric and may be associated with obstruction of the ventricular outflow tract.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:178632406

- Limb-Girdle Muscular Dystrophy, Recessive

  ### Limb-Girdle Muscular Dystrophy, Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:178632406

- Limb-girdle muscular dystrophy, type 2J, Autosomal recessive

  ### Limb-girdle muscular dystrophy, type 2J

  Limb-girdle muscular dystrophy is a term for a group of diseases that cause weakness and wasting of the muscles in the arms and legs. The muscles most affected are those closest to the body (proximal muscles), specifically the muscles of the shoulders, upper arms, pelvic area, and thighs.The severity, age of onset, and features of limb-girdle muscle dystrophy vary among the many subtypes of this condition and may be inconsistent even within the same family. Signs and symptoms may first appear at any age and generally worsen with time, although in some cases they remain mild.In the early stages of limb-girdle muscular dystrophy, affected individuals may have an unusual walking gait, such as waddling or walking on the balls of their feet, and may also have difficulty running. They may need to use their arms to press themselves up from a squatting position because of their weak thigh muscles. As the condition progresses, people with limb-girdle muscular dystrophy may eventually require wheelchair assistance.Muscle wasting may cause changes in posture or in the appearance of the shoulder, back, and arm. In particular, weak shoulder muscles tend to make the shoulder blades (scapulae) "stick out" from the back, a sign known as scapular winging. Affected individuals may also have an abnormally curved lower back (lordosis) or a spine that curves to the side (scoliosis). Some develop joint stiffness (contractures) that can restrict movement in their hips, knees, ankles, or elbows. Overgrowth (hypertrophy) of the calf muscles occurs in some people with limb-girdle muscular dystrophy.Weakening of the heart muscle (cardiomyopathy) occurs in some forms of limb-girdle muscular dystrophy. Some affected individuals experience mild to severe breathing problems related to the weakness of muscles needed for breathing. In some cases, the breathing problems are severe enough that affected individuals need to use a machine to help them breathe (mechanical ventilation).Intelligence is generally unaffected in limb-girdle muscular dystrophy; however, developmental delay and intellectual disability have been reported in rare forms of the disorder.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:178632406

- Myopathy, early-onset, with fatal cardiomyopathy, Autosomal recessive

  ### Myopathy, early-onset, with fatal cardiomyopathy

  Salih myopathy is characterized by muscle weakness (manifest during the neonatal period or in early infancy) and delayed motor development; children acquire independent walking between age 20 months and four years. In the first decade of life, global motor performances are stable or tend to improve. Moderate joint and neck contractures and spinal rigidity may start in the first decade but become more obvious in the second decade. Scoliosis develops after age 11 years. Cardiac dysfunction starts between ages five and 16 years, progresses rapidly, and leads to death between ages eight and 20 years, usually from heart rhythm disturbances.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:178632406

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:178632406

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (3)

Hetero

CT

Gene: TNFSF11
Variant: c.107C>G
(p.Pro36Arg)
rsID: rs138818878
Ref Allele: C
Alt Allele: G
Freq: 1.8508%uncommon
CADD: 9.883

ClinVar Submissions (1)

- Osteopetrosis

  ### Osteopetrosis

  A rare genetic disorder inherited in an autosomal dominant, autosomal recessive, or X-linked recessive pattern. In the majority of cases it is caused by mutations in the CLCN7, TCIRG1, or IKBKG genes. It is characterized by excessive bone formation due to the failure of osteoclasts to resorb bone. It manifests with deformities, fractures, hepatosplenomegaly, anemia, and extramedullary hematopoiesis.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 13:42574410

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (2)

Hetero

CG

Gene: EFEMP1
Variant: c.-464C>T
rsID: rs72811724
Ref Allele: G
Alt Allele: A
Freq: 1.8572%uncommon
CADD: 6.846

ClinVar Submissions (1)

- Doyne honeycomb retinal dystrophy, Autosomal dominant

  ### Doyne honeycomb retinal dystrophy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:55924126

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GA

Gene: MYPN
Variant: c.2410G>A
(p.Gly804Arg)
rsID: rs62620248
Ref Allele: G
Alt Allele: A
Freq: 1.8588%uncommon
CADD: 17.92

ClinVar Submissions (9)

- Cardiovascular phenotype

  ### Cardiovascular phenotype

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 07, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 10:68174502

- Dilated cardiomyopathy 1KK, Autosomal dominant

  ### Dilated cardiomyopathy 1KK

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 07, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 10:68174502

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 07, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 10:68174502

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 07, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 10:68174502

Benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (4)

Hetero

GA

Gene: TMEM138
Variant: c.261G>A
(p.Val87=)
rsID: rs35245221
Ref Allele: G
Alt Allele: A
Freq: 1.8651%uncommon
CADD: 16.74

ClinVar Submissions (7)

- Joubert syndrome

  ### Joubert syndrome

  Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 27, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:61366177

- Joubert syndrome 16, Autosomal recessive

  ### Joubert syndrome 16

  Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 27, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:61366177

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 27, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:61366177

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: BMP1
Variant: c.2115C>T
(p.Asp705=)
rsID: rs61729094
Ref Allele: C
Alt Allele: T
Freq: 1.8683%uncommon
CADD: 16.32

ClinVar Submissions (1)

- Osteogenesis Imperfecta, Recessive

  ### Osteogenesis Imperfecta, Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 8:22201810

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CT

Gene: HGD
Variant: c.1191A>C
(p.Ala397=)
rsID: rs137923025
Ref Allele: T
Alt Allele: G
Freq: 1.8739%uncommon
CADD: 11.59

ClinVar Submissions (1)

- Alkaptonuria, Autosomal recessive

  ### Alkaptonuria

  Alkaptonuria is caused by deficiency of homogentisate 1,2-dioxygenase, an enzyme that converts homogentisic acid (HGA) to maleylacetoacetic acid in the tyrosine degradation pathway. The three major features of alkaptonuria are the presence of HGA in the urine, ochronosis (bluish-black pigmentation in connective tissue), and arthritis of the spine and larger joints. Oxidation of the HGA excreted in the urine produces a melanin-like product and causes the urine to turn dark on standing. Ochronosis occurs only after age 30 years; arthritis often begins in the third decade. Other manifestations include pigment deposition, aortic or mitral valve calcification or regurgitation and occasionally aortic dilatation, renal stones, and prostate stones.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 3:120628527

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

TG

Gene: FKTN
Variant: c.166C>T
(p.Arg56Cys)
rsID: rs41277797
Ref Allele: C
Alt Allele: T
Freq: 1.8763%uncommon
CADD: 27.5

ClinVar Submissions (9)

- Cardiovascular phenotype

  ### Cardiovascular phenotype

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 9
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 9:105601145

- Dilated Cardiomyopathy, Recessive

  ### Dilated Cardiomyopathy, Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 9
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 9:105601145

- Fukuyama congenital muscular dystrophy, Autosomal recessive

  ### Fukuyama congenital muscular dystrophy

  Fukuyama congenital muscular dystrophy (FCMD) is characterized by hypotonia, symmetric generalized muscle weakness, and CNS migration disturbances that result in changes consistent with cobblestone (previously type II) lissencephaly with cerebral and cerebellar cortical dysplasia. Mild, typical, and severe phenotypes are recognized. Onset typically occurs in early infancy, with a poor suck, weak cry, and floppiness. Affected individuals have contractures of the hips, knees, and interphalangeal joints. Later features include myopathic facial appearance, pseudohypertrophy of the calves and forearms, motor and speech retardation, intellectual disability, seizures, ophthalmologic abnormalities including visual impairment and retinal dysplasia, and progressive cardiac involvement in individuals older than age ten years. Swallowing disturbance occurs in individuals with severe FCMD and in individuals older than age ten years, leading to recurrent aspiration pneumonia and death.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 9
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 9:105601145

- Walker-Warburg congenital muscular dystrophy

  ### Walker-Warburg congenital muscular dystrophy

  Walker-Warburg syndrome is an inherited disorder that affects development of the muscles, brain, and eyes. It is the most severe of a group of genetic conditions known as congenital muscular dystrophies, which cause muscle weakness and wasting (atrophy) beginning very early in life. The signs and symptoms of Walker-Warburg syndrome are present at birth or in early infancy. Because of the severity of the problems caused by Walker-Warburg syndrome, most affected individuals do not survive past age 3.Walker-Warburg syndrome affects the skeletal muscles, which are muscles the body uses for movement. Affected babies have weak muscle tone (hypotonia) and are sometimes described as "floppy." The muscle weakness worsens over time.Walker-Warburg syndrome also affects the brain; individuals with this condition typically have a brain abnormality called cobblestone lissencephaly, in which the surface of the brain lacks the normal folds and grooves and instead develops a bumpy, irregular appearance (like that of cobblestones). These individuals may also have a buildup of fluid in the brain (hydrocephalus) or abnormalities of certain parts of the brain, including a region called the cerebellum and the part of the brain that connects to the spinal cord (the brainstem). These changes in the structure of the brain lead to significantly delayed development and intellectual disability. Some individuals with Walker-Warburg syndrome experience seizures.Eye abnormalities are also characteristic of Walker-Warburg syndrome. These can include unusually small eyeballs (microphthalmia), enlarged eyeballs caused by increased pressure in the eyes (buphthalmos), clouding of the lenses of the eyes (cataracts), and problems with the nerve that relays visual information from the eyes to the brain (the optic nerve). These eye problems lead to vision impairment in affected individuals.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 9
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 9:105601145

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 9
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 9:105601145

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (3)

Hetero

CT

Gene: CHD7
Variant: c.2124T>C
(p.Ser708=)
rsID: rs79302359
Ref Allele: T
Alt Allele: C
Freq: 1.8866%uncommon
CADD: 12.26

ClinVar Submissions (7)

- CHARGE association, Autosomal dominant

  ### CHARGE association

  CHARGE is a mnemonic for coloboma, heart defects, choanal atresia, retarded growth and development, genital abnormalities, and ear anomalies. CHARGE syndrome is characterized by the following: Unilateral or bilateral coloboma of the iris, retina-choroid, and/or disc with or without microphthalmos (80%-90% of individuals). Unilateral or bilateral choanal atresia or stenosis (50%-60%). Cranial nerve dysfunction resulting in hyposmia or anosmia, unilateral or bilateral facial palsy (40%), impaired hearing, and/or swallowing problems (70%-90%). Abnormal outer ears, ossicular malformations, Mondini defect of the cochlea and absent or hypoplastic semicircular canals (>90%). Cryptorchidism in males and hypogonadotropic hypogonadism in both males and females. Developmental delay. Cardiovascular malformations (75%-85%). Growth deficiency (70%-80%). Orofacial clefts (15%-20%). Tracheoesophageal fistula (15%-20%). Neonates with CHARGE syndrome often have multiple life-threatening medical conditions. Feeding difficulties are a major cause of morbidity in all age groups.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 07, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 8:60795013

- History of neurodevelopmental disorder

  ### History of neurodevelopmental disorder

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 07, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 8:60795013

- Hypogonadism with anosmia

  ### Hypogonadism with anosmia

  Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) is characterized by inappropriately low serum concentrations of the gonadotropins LH (luteinizing hormone) and FSH (follicle-stimulating hormone) in the presence of low circulating concentrations of sex steroids. IGD is associated with a normal sense of smell (normosmic IGD) in approximately 40% of affected individuals and an impaired sense of smell (Kallmann syndrome) in approximately 60%. IGD can first become apparent in infancy, adolescence, or adulthood. Infant boys with congenital IGD often have micropenis and cryptorchidism. Adolescents and adults with IGD have clinical evidence of hypogonadism and incomplete sexual maturation on physical examination. Adult males with IGD tend to have prepubertal testicular volume (i.e., <4 mL), absence of secondary sexual features (e.g., facial and axillary hair growth, deepening of the voice), decreased muscle mass, diminished libido, erectile dysfunction, and infertility. Adult females have little or no breast development and primary amenorrhea. Although skeletal maturation is delayed, the rate of linear growth is usually normal except for the absence of a distinct pubertal growth spurt.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 07, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 8:60795013

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 07, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 8:60795013

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (4)

Hetero

TC

Gene: FBN2
Variant: c.3015G>A
(p.Leu1005=)
rsID: rs28763946
Ref Allele: C
Alt Allele: T
Freq: 1.901%uncommon
CADD: 2.714

ClinVar Submissions (10)

- Cardiovascular phenotype

  ### Cardiovascular phenotype

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 31, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 10
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:128345559

- Congenital contractural arachnodactyly, Autosomal dominant

  ### Congenital contractural arachnodactyly

  Congenital contractural arachnodactyly (CCA) is characterized by a Marfan-like appearance (tall, slender habitus in which arm span exceeds height) and long, slender fingers and toes (arachnodactyly). Most affected individuals have "crumpled" ears that present as a folded upper helix of the external ear and most have contractures of major joints (knees and ankles) at birth. The proximal interphalangeal joints also have flexion contractures (i.e., camptodactyly), as do the toes. Hip contractures, adducted thumbs, and clubfoot may occur. The majority of affected individuals have muscular hypoplasia. Contractures usually improve with time. Kyphosis/scoliosis is present in about half of all affected individuals. It begins as early as infancy, is progressive, and causes the greatest morbidity in CCA. Dilatation of the aorta is occasionally present. Infants have been observed with a severe/lethal form characterized by multiple cardiovascular and gastrointestinal anomalies in addition to the typical skeletal findings.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 31, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 10
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:128345559

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 31, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 10
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:128345559

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 31, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 10
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:128345559

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (2)

Hetero

CT

Gene: EPG5
Variant: c.3248C>T
(p.Ser1083Leu)
rsID: rs78339727
Ref Allele: G
Alt Allele: A
Freq: 1.9328%uncommon
CADD: 24.1

ClinVar Submissions (1)

- Vici syndrome, Autosomal recessive

  ### Vici syndrome

  Vici syndrome is a rare congenital multisystem disorder characterized by agenesis of the corpus callosum (ACC), cataracts, pigmentary defects, progressive cardiomyopathy, and variable immunodeficiency. Affected individuals also have profound psychomotor retardation and hypotonia due to a myopathy (summary by Finocchi et al., 2012).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 07, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 18:45916574

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GA

Gene: PKHD1
Variant: c.9577G>A
(p.Val3193Ile)
rsID: rs35445653
Ref Allele: C
Alt Allele: T
Freq: 1.944%uncommon
CADD: 0.002

ClinVar Submissions (5)

- Autosomal recessive polycystic kidney disease, Autosomal recessive

  ### Autosomal recessive polycystic kidney disease

  Autosomal recessive polycystic kidney disease (ARPKD) belongs to a group of congenital hepatorenal fibrocystic syndromes and is a cause of significant renal and liver-related morbidity and mortality in children. The majority of individuals with ARPKD present in the neonatal period with enlarged echogenic kidneys. Renal disease is characterized by nephromegaly, hypertension, and varying degrees of renal dysfunction. More than 50% of affected individuals with ARPKD progress to end-stage renal disease (ESRD) within the first decade of life; ESRD may require kidney transplantation. Pulmonary hypoplasia resulting from oligohydramnios occurs in a number of affected infants. Approximately 30% of these infants die in the neonatal period or within the first year of life from respiratory insufficiency or superimposed pulmonary infections. With neonatal respiratory support and renal replacement therapies, the long-term survival of these infants has improved to greater than 80%. As advances in renal replacement therapy and kidney transplantation improve long-term survival, it is likely that clinical hepatobiliary disease will become a major feature of the natural history of ARPKD. In addition, a subset of individuals with this disorder are identified with hepatosplenomegaly; the renal disease is often mild and may be discovered incidentally during imaging studies of the abdomen. Approximately 50% of infants will have clinical evidence of liver involvement at diagnosis although histologic hepatic fibrosis is invariably present at birth. This can lead to progressive portal hypertension with resulting esophageal or gastric varices, enlarged hemorrhoids, splenomegaly, hypersplenism, protein-losing enteropathy, and gastrointestinal bleeding. Other hepatic findings include nonobstructed dilatation of the intrahepatic bile ducts (Caroli syndrome) and dilatation of the common bile duct, which may lead to recurrent or persistent bacterial ascending cholangitis due to dilated bile ducts and stagnant bile flow. An increasing number of affected individuals surviving the neonatal period will eventually require portosystemic shunting or liver transplantation for complications of portal hypertension or cholangitis. The classic neonatal presentation of ARPKD notwithstanding, there is significant variability in age and presenting clinical symptoms related to the relative degree of renal and biliary abnormalities.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 21, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 6:51748039

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 21, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 6:51748039

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 21, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 6:51748039

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: CACNA1S
Variant: c.2063+7G>T
rsID: rs79984703
Ref Allele: C
Alt Allele: A
Freq: 1.9495%uncommon
CADD: 1.705

ClinVar Submissions (5)

- Hypokalemic periodic paralysis

  ### Hypokalemic periodic paralysis

  Hypokalemic periodic paralysis (hypoPP) is a condition in which affected individuals may experience paralytic episodes with concomitant hypokalemia (serum potassium <3.5 mmol/L). The paralytic attacks are characterized by decreased muscle tone (flaccidity) more marked proximally than distally with normal to decreased deep tendon reflexes. The episodes develop over minutes to hours and last several minutes to several days with spontaneous recovery. Some individuals have only one episode in a lifetime; more commonly, crises occur repeatedly: daily, weekly, monthly, or less often. The major triggering factors are cessation of effort following strenuous exercise and carbohydrate-rich evening meals. Additional triggers can include cold, stress/excitement/fear, salt intake, prolonged immobility, use of glucosteroids or alcohol, and anesthetic procedures. The age of onset of the first attack ranges from two to 30 years; the duration of paralytic episodes ranges from one to 72 hours with an average of nearly 24 hours. Long-lasting interictal muscle weakness may occur in some affected individuals and in some stages of the disease and in myopathic muscle changes. A myopathy may occur independent of paralytic symptoms and may be the sole manifestation of hypoPP.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 14, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:201074499

- Hypokalemic periodic paralysis 1, Autosomal dominant

  ### Hypokalemic periodic paralysis 1

  Hypokalemic periodic paralysis (hypoPP) is a condition in which affected individuals may experience paralytic episodes with concomitant hypokalemia (serum potassium <3.5 mmol/L). The paralytic attacks are characterized by decreased muscle tone (flaccidity) more marked proximally than distally with normal to decreased deep tendon reflexes. The episodes develop over minutes to hours and last several minutes to several days with spontaneous recovery. Some individuals have only one episode in a lifetime; more commonly, crises occur repeatedly: daily, weekly, monthly, or less often. The major triggering factors are cessation of effort following strenuous exercise and carbohydrate-rich evening meals. Additional triggers can include cold, stress/excitement/fear, salt intake, prolonged immobility, use of glucosteroids or alcohol, and anesthetic procedures. The age of onset of the first attack ranges from two to 30 years; the duration of paralytic episodes ranges from one to 72 hours with an average of nearly 24 hours. Long-lasting interictal muscle weakness may occur in some affected individuals and in some stages of the disease and in myopathic muscle changes. A myopathy may occur independent of paralytic symptoms and may be the sole manifestation of hypoPP.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 14, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:201074499

- Malignant hyperthermia susceptibility

  ### Malignant hyperthermia susceptibility

  Malignant hyperthermia susceptibility (MHS) is a pharmacogenetic disorder of skeletal muscle calcium regulation associated with uncontrolled skeletal muscle hypermetabolism. Manifestations of malignant hyperthermia (MH) are precipitated by certain volatile anesthetics (i.e., halothane, isoflurane, sevoflurane, desflurane, enflurane), either alone or in conjunction with a depolarizing muscle relaxant (specifically, succinylcholine). The triggering substances release calcium stores from the sarcoplasmic reticulum and may promote entry of calcium from the myoplasm, causing contracture of skeletal muscles, glycogenolysis, and increased cellular metabolism, resulting in production of heat and excess lactate. Affected individuals experience: acidosis, hypercapnia, tachycardia, hyperthermia, muscle rigidity, compartment syndrome, rhabdomyolysis with subsequent increase in serum creatine kinase (CK) concentration, hyperkalemia with a risk for cardiac arrhythmia or even arrest, and myoglobinuria with a risk for renal failure. In nearly all cases, the first manifestations of MH (tachycardia and tachypnea) occur in the operating room; however, MH may also occur in the early postoperative period. There is mounting evidence that some affected individuals will also develop MH with exercise and/or on exposure to hot environments. Without proper and prompt treatment with dantrolene sodium, mortality is extremely high.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 14, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:201074499

- Malignant hyperthermia susceptibility type 5, Autosomal dominant

  ### Malignant hyperthermia susceptibility type 5

  Malignant hyperthermia susceptibility (MHS) is a pharmacogenetic disorder of skeletal muscle calcium regulation associated with uncontrolled skeletal muscle hypermetabolism. Manifestations of malignant hyperthermia (MH) are precipitated by certain volatile anesthetics (i.e., halothane, isoflurane, sevoflurane, desflurane, enflurane), either alone or in conjunction with a depolarizing muscle relaxant (specifically, succinylcholine). The triggering substances release calcium stores from the sarcoplasmic reticulum and may promote entry of calcium from the myoplasm, causing contracture of skeletal muscles, glycogenolysis, and increased cellular metabolism, resulting in production of heat and excess lactate. Affected individuals experience: acidosis, hypercapnia, tachycardia, hyperthermia, muscle rigidity, compartment syndrome, rhabdomyolysis with subsequent increase in serum creatine kinase (CK) concentration, hyperkalemia with a risk for cardiac arrhythmia or even arrest, and myoglobinuria with a risk for renal failure. In nearly all cases, the first manifestations of MH (tachycardia and tachypnea) occur in the operating room; however, MH may also occur in the early postoperative period. There is mounting evidence that some affected individuals will also develop MH with exercise and/or on exposure to hot environments. Without proper and prompt treatment with dantrolene sodium, mortality is extremely high.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 14, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:201074499

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 14, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:201074499

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

CA

Gene: AHI1
Variant: c.2488C>T
(p.Arg830Trp)
rsID: rs13312995
Ref Allele: G
Alt Allele: A
Freq: 1.9631%uncommon
CADD: 24.1

ClinVar Submissions (6)

- Joubert syndrome

  ### Joubert syndrome

  Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 08, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 6:135429886

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 08, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 6:135429886

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OpenSNP
- PubMed (4)

Hetero

GA

Gene: RTTN
Variant: c.578+15G>A
rsID: rs17808334
Ref Allele: C
Alt Allele: T
Freq: 1.9718%uncommon
CADD: 0.309

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 23, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 18:70199399

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CT

Gene: MECP2
Variant: c.378-241C>T
rsID: rs3027931
Ref Allele: G
Alt Allele: A
Freq: 1.9997%uncommon

ClinVar Submissions (1)

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 05, 2002
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: X:154031691

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 05, 2002
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: X:154031691

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Homo

AA

Gene: PKHD1
Variant: c.8950+44A>G
rsID: rs58823342
Ref Allele: T
Alt Allele: C
Freq: 2.0356%uncommon
CADD: 4.543

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 6:51753157

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

TC

Gene: AGL
Variant: c.1185+15T>C
rsID: rs17121466
Ref Allele: T
Alt Allele: C
Freq: 2.0499%uncommon
CADD: 16.5

ClinVar Submissions (4)

- Glycogen storage disease type III, Autosomal recessive

  ### Glycogen storage disease type III

  Glycogen storage disease type III (GSD III) is characterized by variable liver, cardiac muscle, and skeletal muscle involvement. GSD IIIa is the most common subtype, present in about 85% of affected individuals; it manifests with liver and muscle involvement. GSD IIIb, with liver involvement only, comprises about 15% of all GSD III. In infancy and early childhood, liver involvement presents as ketotic hypoglycemia, hepatomegaly, hyperlipidemia, and elevated hepatic transaminases. In adolescence and adulthood, liver disease becomes less prominent. Hypertrophic cardiomyopathy develops in the majority of those with GSD IIIa, usually during childhood. Its clinical significance ranges from asymptomatic in the majority to severe cardiac dysfunction, congestive heart failure, and (rarely) sudden death. Skeletal myopathy manifesting as weakness is not usually evident in childhood, but slowly progresses, typically becoming prominent in the third to fourth decade.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:99875271

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:99875271

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:99875271

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

TC

Gene: SUN2
Variant: c.1042C>T
(p.Arg348Cys)
rsID: rs138708
Ref Allele: G
Alt Allele: A
Freq: 2.0515%uncommon
CADD: 25.4

ClinVar Submissions (1)

- Emery-Dreifuss muscular dystrophy

  ### Emery-Dreifuss muscular dystrophy

  Emery-Dreifuss muscular dystrophy (EDMD) is characterized by the clinical triad of joint contractures that begin in early childhood, slowly progressive muscle weakness and wasting initially in a humero-peroneal distribution that later extends to the scapular and pelvic girdle muscles, and cardiac involvement that may manifest as palpitations, presyncope and syncope, poor exercise tolerance, and congestive heart failure. Age of onset, severity, and progression of muscle and cardiac involvement demonstrate both inter- and intrafamilial variability. Clinical variability ranges from early onset with severe presentation in childhood to late onset with slow progression in adulthood. In general, joint contractures appear during the first two decades, followed by muscle weakness and wasting. Cardiac involvement usually occurs after the second decade.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 17, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 22:38742327

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: DNM1L
Variant: c.*1899C>T
rsID: rs17541634
Ref Allele: C
Alt Allele: T
Freq: 2.061%uncommon
CADD: 0.002

ClinVar Submissions (1)

- Lethal Encephalopathy

  ### Lethal Encephalopathy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 12:32745309

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CT

Gene: DCAF17
Variant: c.*188T>A
rsID: rs142315519
Ref Allele: T
Alt Allele: A
Freq: 2.0746%uncommon
CADD: 2.633

ClinVar Submissions (1)

- Hypogonadism, diabetes mellitus, alopecia, mental retardation and electrocardiographic abnormalities, Autosomal recessive

  ### Hypogonadism, diabetes mellitus, alopecia, mental retardation and electrocardiographic abnormalities

  Neurodegeneration with brain iron accumulation (NBIA) is a group of inherited neurologic disorders in which iron accumulates in the basal ganglia resulting in progressive dystonia, spasticity, parkinsonism, neuropsychiatric abnormalities, and optic atrophy or retinal degeneration. Ten types and their associated genes are recognized. The age of onset ranges from infancy to late adulthood; the rate of progression varies. Cognitive decline occurs in some subtypes, but more often cognition is relatively spared. Cerebellar atrophy is a frequent finding in some subtypes.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 2:171481302

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

TA

Gene: SCN10A
Variant: c.618A>G
(p.Ile206Met)
rsID: rs74717885
Ref Allele: T
Alt Allele: C
Freq: 2.0762%uncommon
CADD: 13.93

ClinVar Submissions (2)

- Brugada syndrome

  ### Brugada syndrome

  Brugada syndrome is characterized by cardiac conduction abnormalities (ST-segment abnormalities in leads V1-V3 on ECG and a high risk for ventricular arrhythmias) that can result in sudden death. Brugada syndrome presents primarily during adulthood although age at diagnosis may range from infancy to late adulthood. The mean age of sudden death is approximately 40 years. Clinical presentations may also include sudden infant death syndrome (SIDS; death of a child during the first year of life without an identifiable cause) and the sudden unexpected nocturnal death syndrome (SUNDS), a typical presentation in individuals from Southeast Asia. Other conduction defects can include first-degree AV block, intraventricular conduction delay, right bundle branch block, and sick sinus syndrome.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 02, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 3:38763578

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 02, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 3:38763578

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

TC

Gene: TMC8
Variant: c.669-4G>C
rsID: rs8079824
Ref Allele: G
Alt Allele: C
Freq: 2.0794%uncommon
CADD: 7.524

ClinVar Submissions (1)

- EPIDERMODYSPLASIA VERRUCIFORMIS, Autosomal recessive

  ### EPIDERMODYSPLASIA VERRUCIFORMIS

  Epidermodysplasia verruciformis (EV) is a rare genodermatosis associated with a high risk of skin cancer. EV results from an abnormal susceptibility to specific related human papillomavirus (HPV) genotypes and to the oncogenic potential of some of them, mainly HPV5. Infection with EV-associated HPV leads to the early development of disseminated flat wart-like and pityriasis versicolor-like lesions. Patients are unable to reject their lesions, and cutaneous Bowen carcinomas in situ and invasive squamous cell carcinomas develop in about half of them, mainly on sun-exposed areas (summary by Ramoz et al., 2000). Genetic Heterogeneity of Susceptibility to Epidermodysplasia Verruciformis Susceptibility to EV2 (618231) is conferred by mutation in the TMC8 gene (605829) on chromosome 17q25; EV3 (618267) by mutation in the CIB1 gene (602293) on chromosome 15q26; EV4 (618307) by mutation in the RHOH gene (602037) on chromosome 4p13; and EV5 (618309) by mutation in the IL7 gene (146660) on chromosome 8q12.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 11, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 17:78133849

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GC

Gene: CLDN19
Variant: c.*1018G>T
rsID: rs114944537
Ref Allele: C
Alt Allele: A
Freq: 2.0977%uncommon
CADD: 1.291

ClinVar Submissions (1)

- Renal Hypomagnesemia, Recessive

  ### Renal Hypomagnesemia, Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:42734068

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CA

Gene: EPCAM
Variant: c.492-5T>C
rsID: rs78608315
Ref Allele: T
Alt Allele: C
Freq: 2.1463%uncommon
CADD: 17.34

ClinVar Submissions (6)

- Hereditary cancer-predisposing syndrome

  ### Hereditary cancer-predisposing syndrome

  The condition of a pattern of malignancies within a family, but not every individual's necessarily having the same neoplasm. Characteristically the tumor tends to occur at an earlier than average age, individuals may have more than one primary tumor, the tumors may be multicentric, usually more than 25 percent of the individuals in direct lineal descent from the proband are affected, and the cancer predisposition in these families behaves as an autosomal dominant trait with about 60 percent penetrance.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 27, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:47377009

- Hereditary nonpolyposis colon cancer

  ### Hereditary nonpolyposis colon cancer

  A group of autosomal-dominant inherited diseases in which COLON CANCER arises in discrete adenomas. Unlike FAMILIAL POLYPOSIS COLI with hundreds of polyps, hereditary nonpolyposis colorectal neoplasms occur much later, in the fourth and fifth decades. HNPCC has been associated with germline mutations in mismatch repair (MMR) genes. It has been subdivided into Lynch syndrome I or site-specific colonic cancer, and LYNCH SYNDROME II which includes extracolonic cancer.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 27, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:47377009

- Lynch syndrome

  ### Lynch syndrome

  Lynch syndrome is characterized by an increased risk for colorectal cancer (CRC) and cancers of the endometrium, stomach, ovary, small bowel, hepatobiliary tract, urinary tract, brain, and skin. In individuals with Lynch syndrome the following lifetime risks for cancer are seen: CRC: 52%-82% (mean age at diagnosis 44-61 years). Endometrial cancer in females: 25%-60% (mean age at diagnosis 48-62 years). Gastric cancer: 6%-13% (mean age at diagnosis 56 years). Ovarian cancer: 4%-12% (mean age at diagnosis 42.5 years; ~30% are diagnosed < age 40 years). The risk for other Lynch syndrome-related cancers is lower, though substantially increased over general population rates.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 27, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:47377009

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 27, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:47377009

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

TC

Gene: CYP7B1
Variant: c.*337T>G
rsID: rs118000312
Ref Allele: A
Alt Allele: C
Freq: 2.1534%uncommon
CADD: 3.598

ClinVar Submissions (1)

- Congenital Bile Acid Synthesis Defect

  ### Congenital Bile Acid Synthesis Defect

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 8:64596305

- Spastic Paraplegia, Recessive

  ### Spastic Paraplegia, Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 8:64596305

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

AC

Gene: DIAPH1
Variant: c.3579C>T
(p.Gly1193=)
rsID: rs2302102
Ref Allele: G
Alt Allele: A
Freq: 2.1614%uncommon
CADD: 4.458

ClinVar Submissions (5)

- Deafness, autosomal dominant 1, Autosomal dominant

  ### Deafness, autosomal dominant 1

  DFNA1 is an autosomal dominant form of progressive hearing loss with onset in the first decade. Some patients may have mild thrombocytopenia and enlarged platelets, although most of these individuals do not have significant bleeding tendencies (summary by Neuhaus et al., 2017).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 31, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:141524225

- Nonsyndromic Hearing Loss, Mixed

  ### Nonsyndromic Hearing Loss, Mixed

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 31, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:141524225

- Seizures, cortical blindness, and microcephaly syndrome, Autosomal recessive

  ### Seizures, cortical blindness, and microcephaly syndrome

  Seizures, cortical blindness, and microcephaly syndrome (SCBMS) is an autosomal recessive neurodevelopmental disorder characterized by microcephaly, early-onset seizures, severely delayed psychomotor development, and cortical blindness. Affected individuals also tend to show poor overall growth with short stature (summary by Ercan-Sencicek et al., 2015).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 31, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:141524225

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 31, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:141524225

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (2)

Hetero

GA

Gene: KANSL1;MAPT
Variant: c.*2810G>A
rsID: rs2158256
Ref Allele: G
Alt Allele: A
Freq: 2.1654%uncommon
CADD: 3.774

ClinVar Submissions (1)

- MAPT-Related Spectrum Disorders

  ### MAPT-Related Spectrum Disorders

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 17:46026981

- Syndromic intellectual disability

  ### Syndromic intellectual disability

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 17:46026981

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: GABRA1
Variant: c.*1929T>C
rsID: rs2290733
Ref Allele: T
Alt Allele: C
Freq: 2.1861%uncommon
CADD: 13.69

ClinVar Submissions (1)

- Juvenile myoclonic epilepsy, Autosomal dominant

  ### Juvenile myoclonic epilepsy

  Juvenile myoclonic epilepsy is a subtype of idiopathic generalized epilepsy (EIG; see 600669) affecting up to 26% of all individuals with EIG. Individuals with JME have afebrile seizures only, with onset in adolescence of myoclonic jerks. Myoclonic jerks occur usually in the morning (Janz and Durner, 1997). Genetic Heterogeneity of Juvenile Myoclonic Seizures Susceptibility to EJM can be conferred by variation in several other genes: EJM5 (611136), by variation in the GABRA1 gene (137160) on 5q34; EJM6 (see 607682), by variation in the CACNB4 gene (601949) on 2q23; EJM7 (see 613060), by variation in the GABRD gene (137163) on 1p36; EJM8 (see 607628), by variation in the CLCN2 gene (600570) on 3q27; and EJM10 (617924), by variation in the ICK gene (612325) on chromosome 6p12. In addition, EJM loci have been identified by linkage analysis: EJM2 (see 604827) on 15q14, EJM3 (608816) on 6p21, EJM4 (611364) on 5q12-q14, and EJM9 (614280) on 2q33-q36.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:161899351

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

TC

Gene: KRAS
Variant: c.*3502T>A
rsID: rs61764372
Ref Allele: A
Alt Allele: T
Freq: 2.198%uncommon
CADD: 17.53

ClinVar Submissions (1)

- Cardio-facio-cutaneous syndrome, Autosomal dominant

  ### Cardio-facio-cutaneous syndrome

  Cardiofaciocutaneous (CFC) syndrome is characterized by cardiac abnormalities (pulmonic stenosis and other valve dysplasias, septal defects, hypertrophic cardiomyopathy, rhythm disturbances), distinctive craniofacial appearance, and cutaneous abnormalities (including xerosis, hyperkeratosis, ichthyosis, keratosis pilaris, ulerythema ophryogenes, eczema, pigmented moles, hemangiomas, and palmoplantar hyperkeratosis). The hair is typically sparse, curly, fine or thick, woolly or brittle; eyelashes and eyebrows may be absent or sparse. Nails may be dystrophic or fast growing. Some form of neurologic and/or cognitive delay (ranging from mild to severe) is seen in all affected individuals. Neoplasia, mostly acute lymphoblastic leukemia (ALL), has been reported in some individuals.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 12:25206293

- Noonan syndrome

  ### Noonan syndrome

  Noonan syndrome (NS) is characterized by characteristic facies, short stature, congenital heart defect, and developmental delay of variable degree. Other findings can include broad or webbed neck, unusual chest shape with superior pectus carinatum and inferior pectus excavatum, cryptorchidism, varied coagulation defects, lymphatic dysplasias, and ocular abnormalities. Although birth length is usually normal, final adult height approaches the lower limit of normal. Congenital heart disease occurs in 50%-80% of individuals. Pulmonary valve stenosis, often with dysplasia, is the most common heart defect and is found in 20%-50% of individuals. Hypertrophic cardiomyopathy, found in 20%-30% of individuals, may be present at birth or develop in infancy or childhood. Other structural defects include atrial and ventricular septal defects, branch pulmonary artery stenosis, and tetralogy of Fallot. Up to one fourth of affected individuals have mild intellectual disability, and language impairments in general are more common in NS than in the general population.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 12:25206293

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

AT

Gene: TMEM70
Variant: c.*904A>G
rsID: rs59024088
Ref Allele: A
Alt Allele: G
Freq: 2.2084%uncommon
CADD: 5.637

ClinVar Submissions (1)

- Mitochondrial Complex V (ATP Synthase) Deficiency, Nuclear Type

  ### Mitochondrial Complex V (ATP Synthase) Deficiency, Nuclear Type

  Mitochondrial complex V deficiency is a shortage (deficiency) of a protein complex called complex V or a loss of its function. Complex V is found in cell structures called mitochondria, which convert the energy from food into a form that cells can use. Complex V is the last of five mitochondrial complexes that carry out a multistep process called oxidative phosphorylation, through which cells derive much of their energy.Mitochondrial complex V deficiency can cause a wide variety of signs and symptoms affecting many organs and systems of the body, particularly the nervous system and the heart. The disorder can be life-threatening in infancy or early childhood. Affected individuals may have feeding problems, slow growth, low muscle tone (hypotonia), extreme fatigue (lethargy), and developmental delay. They tend to develop elevated levels of lactic acid in the blood (lactic acidosis), which can cause nausea, vomiting, weakness, and rapid breathing. High levels of ammonia in the blood (hyperammonemia) can also occur in affected individuals, and in some cases result in abnormal brain function (encephalopathy) and damage to other organs.Another common feature of mitochondrial complex V deficiency is hypertrophic cardiomyopathy. This condition is characterized by thickening (hypertrophy) of the heart (cardiac) muscle that can lead to heart failure. People with mitochondrial complex V deficiency may also have a characteristic pattern of facial features, including a high forehead, curved eyebrows, outside corners of the eyes that point downward (downslanting palpebral fissures), a prominent bridge of the nose, low-set ears, thin lips, and a small chin (micrognathia).Some people with mitochondrial complex V deficiency have groups of signs and symptoms that are classified as a specific syndrome. For example, mitochondrial complex V deficiency can cause a condition called neuropathy, ataxia, and retinitis pigmentosa (NARP). NARP causes a variety of signs and symptoms chiefly affecting the nervous system. Beginning in childhood or early adulthood, most people with NARP experience numbness, tingling, or pain in the arms and legs (sensory neuropathy); muscle weakness; and problems with balance and coordination (ataxia). Many affected individuals also have cognitive impairment and an eye disorder called retinitis pigmentosa that causes vision loss.A condition called Leigh syndrome can also be caused by mitochondrial complex V deficiency. Leigh syndrome is characterized by progressive loss of mental and movement abilities (developmental or psychomotor regression) and typically results in death within 2 to 3 years after the onset of symptoms. Both NARP and Leigh syndrome can also have other causes.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 8:73982525

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

AG

Gene: TRPM4
Variant: c.267+14C>G
rsID: rs113040724
Ref Allele: C
Alt Allele: G
Freq: 2.2147%uncommon
CADD: 10.53

ClinVar Submissions (2)

- Progressive familial heart block

  ### Progressive familial heart block

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 10, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 19:49166229

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 10, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 19:49166229

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CG

Gene: IRAK4
Variant: c.*2704C>T
rsID: rs4251562
Ref Allele: C
Alt Allele: T
Freq: 2.2315%uncommon
CADD: 5.807

ClinVar Submissions (1)

- IRAK4 deficiency, Autosomal recessive

  ### IRAK4 deficiency

  IRAK4 deficiency is an autosomal recessive primary immunodeficiency that impairs Toll (see TLR4; 603030)/IL1R (see IL1R1; 147810) immunity, except for the TLR3 (603029)- and TLR4-interferon-alpha (IFNA; 147660)/beta (IFNB; 147640) pathways (Ku et al., 2007).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 12:43789419

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: WDR35
Variant: c.*2836C>T
rsID: rs74469198
Ref Allele: G
Alt Allele: A
Freq: 2.2362%uncommon
CADD: 2.799

ClinVar Submissions (1)

- Cranioectodermal dysplasia

  ### Cranioectodermal dysplasia

  Cranioectodermal dysplasia (CED), a ciliopathy also known as Sensenbrenner syndrome, is a multisystem disorder with skeletal involvement (narrow thorax, shortened proximal limbs, and brachydactyly), ectodermal features (widely-spaced hypoplastic teeth, hypodontia, sparse hair, skin laxity, abnormal nails), joint laxity, growth retardation, and characteristic facial features (frontal bossing, low-set simple ears, high forehead, telecanthus/epicanthus, full cheeks, everted lower lip). Most affected children develop nephronophthisis that often leads to end-stage renal disease (ESRD) in infancy or childhood, a major cause of morbidity and mortality. Hepatic fibrosis and retinal dystrophy, other manifestations of ciliopathies, are also observed. Dolichocephaly, often secondary to sagittal craniosynostosis, is a primary manifestation that distinguishes CED from most other ciliopathies. Brain malformations and developmental delay may also occur.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:19910722

- Short Rib Polydactyly Syndrome

  ### Short Rib Polydactyly Syndrome

  A rare congenital lethal syndrome characterized by the presence of extra fingers and toes and short ribs, the latter resulting in inability of the lungs to expand. The newborn dies shortly after birth.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:19910722

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: PTCH1
Variant: c.735A>G
(p.Thr245=)
rsID: rs1805154
Ref Allele: T
Alt Allele: C
Freq: 2.2506%uncommon
CADD: 15.15

ClinVar Submissions (5)

- Gorlin syndrome, Autosomal dominant

  ### Gorlin syndrome

  Nevoid basal cell carcinoma syndrome (NBCCS) is characterized by the development of multiple jaw keratocysts, frequently beginning in the second decade of life, and/or basal cell carcinomas (BCCs) usually from the third decade onward. Approximately 60% of individuals have a recognizable appearance with macrocephaly, frontal bossing, coarse facial features, and facial milia. Most individuals have skeletal anomalies (e.g., bifid ribs, wedge-shaped vertebrae). Ectopic calcification, particularly in the falx, is present in more than 90% of affected individuals by age 20 years. Cardiac and ovarian fibromas occur in approximately 2% and 20% of individuals respectively. Approximately 5% of all children with NBCCS develop medulloblastoma (primitive neuroectodermal tumor), generally the desmoplastic subtype. The risk of developing medulloblastoma is substantially higher in individuals with an SUFU pathogenic variant (33%) than in those with a PTCH1 pathogenic variant (<2%). Peak incidence is at age one to two years. Life expectancy in NBCCS is not significantly different from average.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 11, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 9:95481960

- Hereditary cancer-predisposing syndrome

  ### Hereditary cancer-predisposing syndrome

  The condition of a pattern of malignancies within a family, but not every individual's necessarily having the same neoplasm. Characteristically the tumor tends to occur at an earlier than average age, individuals may have more than one primary tumor, the tumors may be multicentric, usually more than 25 percent of the individuals in direct lineal descent from the proband are affected, and the cancer predisposition in these families behaves as an autosomal dominant trait with about 60 percent penetrance.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 11, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 9:95481960

- Holoprosencephaly sequence

  ### Holoprosencephaly sequence

  Holoprosencephaly (HPE) is a structural anomaly of the brain in which there is failed or incomplete separation of the forebrain early in gestation. Classic HPE encompasses a continuum of brain malformations including (in order of decreasing severity): alobar, semilobar, lobar, and middle interhemispheric variant (MIHV) type HPE; a septopreoptic type has also been described. Other CNS abnormalities not specific to HPE may also occur. HPE is accompanied by a spectrum of characteristic craniofacial anomalies in approximately 80% of individuals with HPE. Developmental delay is present in virtually all individuals with the HPE spectrum of CNS anomalies. Seizures and pituitary dysfunction are common. Most affected fetuses do not survive; severely affected children typically do not survive beyond early infancy, while a significant proportion of more mildly affected children survive past 12 months. Mildly manifesting individuals without appreciable brain anomalies on conventional neuroimaging may be described as having "microform" HPE.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 11, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 9:95481960

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 11, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 9:95481960

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 11, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 9:95481960

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

TC

Gene: ACTN2
Variant: c.-22C>T
rsID: rs138279482
Ref Allele: C
Alt Allele: T
Freq: 2.2522%uncommon
CADD: 17.7

ClinVar Submissions (4)

- Dilated Cardiomyopathy, Dominant

  ### Dilated Cardiomyopathy, Dominant

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:236686652

- Dilated cardiomyopathy 1AA, Autosomal dominant

  ### Dilated cardiomyopathy 1AA

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:236686652

- Hypertrophic cardiomyopathy

  ### Hypertrophic cardiomyopathy

  A condition in which the myocardium is hypertrophied without an obvious cause. The hypertrophy is generally asymmetric and may be associated with obstruction of the ventricular outflow tract.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:236686652

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:236686652

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CT

Gene: KL
Variant: c.*1286A>G
rsID: rs41292181
Ref Allele: A
Alt Allele: G
Freq: 2.2546%uncommon
CADD: 12.14

ClinVar Submissions (1)

- Tumoral calcinosis, familial, hyperphosphatemic, Autosomal recessive

  ### Tumoral calcinosis, familial, hyperphosphatemic

  Hyperphosphatemic familial tumoral calcinosis (HFTC) is characterized by: Ectopic calcifications (tumoral calcinosis) typically found in periarticular soft tissues exposed to repetitive trauma or prolonged pressure (e.g., hips, elbows, and shoulders); and Painful swellings (referred to as hyperostosis) in the areas overlying the diaphyses of the tibiae (and less often the ulna, metacarpal bones, and radius). The dental phenotype unique to HFTC includes enamel hypoplasia, short and bulbous roots, obliteration of pulp chambers and canals, and pulp stones. Less common are large and small vessel calcifications that are often asymptomatic incidental findings on radiologic studies but can also cause peripheral vascular insufficiency (e.g., pain, cold extremities, and decreased peripheral pulses). Less frequently reported findings include testicular microlithiasis and angioid streaks of the retina.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 13:33065472

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

AG

Gene: DEPDC5
Variant: c.3358A>G
(p.Met1120Val)
rsID: rs61731662
Ref Allele: A
Alt Allele: G
Freq: 2.2657%uncommon
CADD: 1.267

ClinVar Submissions (4)

- Epilepsy, familial focal, with variable foci 1, Autosomal dominant

  ### Epilepsy, familial focal, with variable foci 1

  DEPDC5-related epilepsy encompasses a range of epilepsy syndromes, almost all of which are characterized by focal seizures, with seizure onset in a discrete area of the brain. While most individuals with DEPDC5-related epilepsy have a normal brain MRI, some have epilepsy associated with a cortical malformation, usually focal cortical dysplasia. Seizure syndromes include familial focal epilepsy with variable foci (FFEVF), autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), familial mesial temporal lobe epilepsies (FMTLE), autosomal dominant epilepsy with auditory features (ADEAF), and infantile spasms. Although psychomotor development is usually normal, intellectual disability or autism spectrum disorder has been reported in some individuals.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 04, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 22:31870617

- Seizures

  ### Seizures

  Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or "seizure disorder."

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 04, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 22:31870617

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 04, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 22:31870617

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 04, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 22:31870617

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (2)

Hetero

AG

Gene: SH3TC2
Variant: c.*14411G>A
rsID: rs143623684
Ref Allele: C
Alt Allele: T
Freq: 2.2729%uncommon
CADD: 0.37

ClinVar Submissions (1)

- Charcot-Marie-Tooth disease type 4

  ### Charcot-Marie-Tooth disease type 4

  Charcot-Marie-Tooth disease type 4 (CMT4) belongs to the genetically heterogeneous group of CMT peripheral sensorimotor polyneuropathy diseases. Type 4 is less common and often limited to certain ethnic groups. Patients present with the typical CMT phenotype along with typical features of progressive, distally accentuated weakness and atrophy of muscles innervated by the peroneal nerve in the lower limbs, followed by weakness and atrophy of hands, sensory loss, and characteristic foot abnormalities.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 5:148990300

- Mononeuropathy of the Median Nerve

  ### Mononeuropathy of the Median Nerve

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 5:148990300

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CT

Gene: GALT
Variant: c.652C>T
(p.Leu218=)
rsID: rs2070075
Ref Allele: C
Alt Allele: T
Freq: 2.2888%uncommon
CADD: 15.26

ClinVar Submissions (9)

- Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase

  ### Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 11, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign, other
  Assembly: GRCh38
  Chromosome/Position: 9:34648421
  OMIM Allelic Variant: 606999.0012

- GALT POLYMORPHISM (LOS ANGELES, D1)

  ### GALT POLYMORPHISM (LOS ANGELES, D1)

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 11, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign, other
  Assembly: GRCh38
  Chromosome/Position: 9:34648421
  OMIM Allelic Variant: 606999.0012

- Galactosemia

  ### Galactosemia

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 11, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign, other
  Assembly: GRCh38
  Chromosome/Position: 9:34648421
  OMIM Allelic Variant: 606999.0012

- not provided

  ### not provided

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 11, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign, other
  Assembly: GRCh38
  Chromosome/Position: 9:34648421
  OMIM Allelic Variant: 606999.0012

Expert Reviewed Benign/Likely benign, other

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (10)

Hetero

CT

Gene: NRG1
Variant: c.397G>C
(p.Val133Leu)
rsID: rs35641374
Ref Allele: G
Alt Allele: C
Freq: 2.3031%uncommon
CADD: 16.42

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 06, 2015
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 8:32648114

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (2)

Hetero

GC

Gene: RHO
Variant: c.*313C>T
rsID: rs55941599
Ref Allele: C
Alt Allele: T
Freq: 2.3063%uncommon
CADD: 16.43

ClinVar Submissions (1)

- Congenital Stationary Night Blindness, Dominant

  ### Congenital Stationary Night Blindness, Dominant

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 3:129534031

- Retinitis Pigmentosa, Dominant/Recessive

  ### Retinitis Pigmentosa, Dominant/Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 3:129534031

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CT

Gene: PDGFRB
Variant: c.1854G>A
(p.Thr618=)
rsID: rs56072663
Ref Allele: C
Alt Allele: T
Freq: 2.3223%uncommon
CADD: 1.616

ClinVar Submissions (1)

- Basal ganglia calcification, idiopathic, 4, Autosomal dominant

  ### Basal ganglia calcification, idiopathic, 4

  Primary familial brain calcification (PFBC) is a neurodegenerative disorder with characteristic calcium deposits in the basal ganglia and other brain areas visualized on neuroimaging. Most affected individuals are in good health during childhood and young adulthood and typically present in the fourth to fifth decade with a gradually progressive movement disorder and neuropsychiatric symptoms. The movement disorder first manifests as clumsiness, fatigability, unsteady gait, slow or slurred speech, dysphagia, involuntary movements, or muscle cramping. Neuropsychiatric symptoms, often the first or most prominent manifestations, range from mild difficulty with concentration and memory to changes in personality and/or behavior, to psychosis and dementia. Seizures of various types occur frequently, some individuals experience chronic headache and vertigo; urinary urgency or incontinence may be present.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 19, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 5:150124785

- Infantile myofibromatosis 1, Autosomal dominant

  ### Infantile myofibromatosis 1

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 19, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 5:150124785

- Kosaki overgrowth syndrome, Autosomal dominant

  ### Kosaki overgrowth syndrome

  Kosaki overgrowth syndrome is characterized by a facial gestalt involving prominent forehead, proptosis, downslanting palpebral fissures, wide nasal bridge, thin upper lip, and pointed chin. Affected individuals are tall, with an elongated lower segment, hands, and feet. Skin is hyperelastic and fragile, and there is progressive neurologic deterioration with white matter lesions on brain imaging (Takenouchi et al., 2015).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 19, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 5:150124785

- Premature aging syndrome, Penttinen type, Autosomal dominant

  ### Premature aging syndrome, Penttinen type

  Penttinen syndrome is characterized by a prematurely aged appearance involving lipoatrophy and epidermal and dermal atrophy, as well as hypertrophic lesions that resemble scars, thin hair, proptosis, underdeveloped cheekbones, and marked acroosteolysis (Johnston et al., 2015).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 19, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 5:150124785

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CT

Gene: MSH2
Variant: c.1760-62G>A
rsID: rs17218439
Ref Allele: G
Alt Allele: A
Freq: 2.3246%uncommon
CADD: 1.294

ClinVar Submissions (3)

- Hereditary cancer-predisposing syndrome

  ### Hereditary cancer-predisposing syndrome

  The condition of a pattern of malignancies within a family, but not every individual's necessarily having the same neoplasm. Characteristically the tumor tends to occur at an earlier than average age, individuals may have more than one primary tumor, the tumors may be multicentric, usually more than 25 percent of the individuals in direct lineal descent from the proband are affected, and the cancer predisposition in these families behaves as an autosomal dominant trait with about 60 percent penetrance.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 04, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 2:47474963

- Lynch syndrome

  ### Lynch syndrome

  Lynch syndrome is characterized by an increased risk for colorectal cancer (CRC) and cancers of the endometrium, stomach, ovary, small bowel, hepatobiliary tract, urinary tract, brain, and skin. In individuals with Lynch syndrome the following lifetime risks for cancer are seen: CRC: 52%-82% (mean age at diagnosis 44-61 years). Endometrial cancer in females: 25%-60% (mean age at diagnosis 48-62 years). Gastric cancer: 6%-13% (mean age at diagnosis 56 years). Ovarian cancer: 4%-12% (mean age at diagnosis 42.5 years; ~30% are diagnosed < age 40 years). The risk for other Lynch syndrome-related cancers is lower, though substantially increased over general population rates.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 04, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 2:47474963

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 04, 2016
  Review Status: reviewed by expert panel
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 2:47474963

Expert Reviewed Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: WFS1
Variant: c.*567C>G
rsID: rs12508118
Ref Allele: C
Alt Allele: G
Freq: 2.3525%uncommon
CADD: 0.648

ClinVar Submissions (1)

- Nonsyndromic Hearing Loss, Dominant

  ### Nonsyndromic Hearing Loss, Dominant

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 4:6303035

- WFS1-Related Spectrum Disorders

  ### WFS1-Related Spectrum Disorders

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 4:6303035

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CG

Gene: KCNH5
Variant: c.2088G>A
(p.Val696=)
rsID: rs36004050
Ref Allele: C
Alt Allele: T
Freq: 2.3541%uncommon
CADD: 7.874

ClinVar Submissions (1)

- Early infantile epileptic encephalopathy

  ### Early infantile epileptic encephalopathy

  A neurological disorder characterized by recurring seizures presenting within the first three months of life and progressive cerebral dysfunction.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 03, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 14:62708387

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CT

Gene: RBM20
Variant: c.1801-11G>C
rsID: rs12572941
Ref Allele: G
Alt Allele: C
Freq: 2.4019%uncommon
CADD: 16.83

ClinVar Submissions (5)

- Dilated Cardiomyopathy, Dominant

  ### Dilated Cardiomyopathy, Dominant

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 10:110810372

- Dilated cardiomyopathy 1DD, Autosomal dominant

  ### Dilated cardiomyopathy 1DD

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 10:110810372

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 10:110810372

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (2)

Hetero

GC

Gene: TCN2
Variant: c.1023G>A
(p.Pro341=)
rsID: rs76802001
Ref Allele: G
Alt Allele: A
Freq: 2.421%uncommon
CADD: 0.027

ClinVar Submissions (2)

- Transcobalamin II deficiency, Autosomal recessive

  ### Transcobalamin II deficiency

  Transcobalamin II deficiency is an autosomal recessive disorder with onset in early infancy characterized by failure to thrive, megaloblastic anemia, and pancytopenia. Other features include methylmalonic aciduria, recurrent infections, and vomiting and diarrhea. Treatment with cobalamin results in clinical improvement, but the untreated disorder may result in mental retardation and neurologic abnormalities (summary by Haberle et al., 2009). Hall (1981) gave a clinically oriented review of congenital defects of vitamin B12 transport, and Frater-Schroder (1983) gave a genetically oriented review.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 31, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 22:30617412

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GA

Gene: ABAT
Variant: c.*1501A>G
rsID: rs17651562
Ref Allele: A
Alt Allele: G
Freq: 2.4218%uncommon
CADD: 3.712

ClinVar Submissions (1)

- Gamma-aminobutyric acid transaminase deficiency, Autosomal recessive

  ### Gamma-aminobutyric acid transaminase deficiency

  GABA-transaminase deficiency is characterized by neonatal or early infantile-onset encephalopathy, hypotonia, hypersomnolence, epilepsy, choreoathetosis, and accelerated linear growth. Electroencephalograms show burst-suppression, modified hypsarrhythmia, multifocal spikes, and generalized spike-wave. Severity varies, but most patients have profound developmental impairment and some patients die in infancy (summary by Koenig et al., 2017).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 16:8782931

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

AG

Gene: NFU1
Variant: c.286C>T
(p.Arg96Cys)
rsID: rs74637005
Ref Allele: G
Alt Allele: A
Freq: 2.4505%uncommon
CADD: 23.1

ClinVar Submissions (3)

- Multiple mitochondrial dysfunctions syndrome

  ### Multiple mitochondrial dysfunctions syndrome

  Syndrome caused by impairment of mitochondria. Whilst mitochondrial disorders may be caused by impairment of a single stage of energy production, individuals with multiple mitochondrial dysfunctions syndrome have reduced function of more than one stage. Symptoms begin in early life and affected individuals usually do not live past infancy. Symptoms include encephalopathy, hypotonia, seizures and psychomotor delay. Most affected babies have lactic acidosis that can be life threatening.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:69423598

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:69423598

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:69423598

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: NSD1
Variant: c.3106G>C
(p.Ala1036Pro)
rsID: rs28932179
Ref Allele: G
Alt Allele: C
Freq: 2.4568%uncommon
CADD: 9.476

ClinVar Submissions (7)

- Beckwith-Wiedemann syndrome, Autosomal dominant

  ### Beckwith-Wiedemann syndrome

  Beckwith-Wiedemann syndrome (BWS) is a growth disorder variably characterized by neonatal hypoglycemia, macrosomia, macroglossia, hemihyperplasia, omphalocele, embryonal tumors (e.g., Wilms tumor, hepatoblastoma, neuroblastoma, and rhabdomyosarcoma), visceromegaly, adrenocortical cytomegaly, renal abnormalities (e.g., medullary dysplasia, nephrocalcinosis, medullary sponge kidney, and nephromegaly), and ear creases/pits. BWS is considered a clinical spectrum, in which affected individuals may have many of these features or may have only one or two clinical features. Early death may occur from complications of prematurity, hypoglycemia, cardiomyopathy, macroglossia, or tumors. However, the previously reported mortality of 20% is likely an overestimate given better recognition of the disorder along with enhanced treatment options. Macroglossia and macrosomia are generally present at birth but may have postnatal onset. Growth rate slows around age seven to eight years. Hemihyperplasia may affect segmental regions of the body or selected organs and tissues.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 26, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:177211505

- History of neurodevelopmental disorder

  ### History of neurodevelopmental disorder

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 26, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:177211505

- Sotos syndrome

  ### Sotos syndrome

  Sotos syndrome is a disorder characterized by a distinctive facial appearance, overgrowth in childhood, and learning disabilities or delayed development of mental and movement abilities. Characteristic facial features include a long, narrow face; a high forehead; flushed (reddened) cheeks; and a small, pointed chin. In addition, the outside corners of the eyes may point downward (down-slanting palpebral fissures). This facial appearance is most notable in early childhood. Affected infants and children tend to grow quickly; they are significantly taller than their siblings and peers and have an unusually large head. However, adult height is usually in the normal range.People with Sotos syndrome often have intellectual disability, and most also have behavioral problems. Frequent behavioral issues include attention deficit hyperactivity disorder (ADHD), phobias, obsessions and compulsions, tantrums, and impulsive behaviors. Problems with speech and language are also common. Affected individuals often have a stutter, a monotone voice, and problems with sound production. Additionally, weak muscle tone (hypotonia) may delay other aspects of early development, particularly motor skills such as sitting and crawling.Other signs and symptoms of Sotos syndrome can include an abnormal side-to-side curvature of the spine (scoliosis), seizures, heart or kidney defects, hearing loss, and problems with vision. Some infants with this disorder experience yellowing of the skin and whites of the eyes (jaundice) and poor feeding.A small percentage of people with Sotos syndrome have developed cancer, most often in childhood, but no single form of cancer occurs most frequently with this condition. It remains uncertain whether Sotos syndrome increases the risk of specific types of cancer. If people with this disorder have an increased cancer risk, it is only slightly greater than that of the general population.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 26, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:177211505

- Weaver syndrome, Autosomal dominant

  ### Weaver syndrome

  EZH2-related overgrowth includes EZH2-related Weaver syndrome at one end of the spectrum and tall stature at the other. Although most individuals diagnosed with a heterozygous EZH2 pathogenic variant have been identified because of a clinical suspicion of Weaver syndrome, a minority have been identified through molecular genetic testing of family members of probands or individuals with overgrowth who did not have a clinical diagnosis of Weaver syndrome. Thus, the extent of the phenotypic spectrum associated with a heterozygous EZH2 pathogenic variant is not yet known. Weaver syndrome is characterized by tall stature, variable intellect (ranging from normal intellect to severe intellectual disability), characteristic facial appearance, and a range of associated clinical features including advanced bone age, poor coordination, soft doughy skin, camptodactyly of the fingers and/or toes, umbilical hernia, abnormal tone, and hoarse low cry in infancy. Brain MRI has identified abnormalities in a few individuals with EZH2-related overgrowth. Neuroblastoma occurs at a slightly increased frequency in individuals with a heterozygous EZH2 pathogenic variant but data are insufficient to determine absolute risk. There is currently no evidence that additional malignancies (including hematologic malignancies) occur with increased frequency.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 26, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:177211505

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 26, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:177211505

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (3)

Hetero

GC

Gene: XDH
Variant: c.514G>A
(p.Gly172Arg)
rsID: rs45523133
Ref Allele: C
Alt Allele: T
Freq: 2.46%uncommon
CADD: 16.79

ClinVar Submissions (1)

- Xanthinuria

  ### Xanthinuria

  An increased concentration of xanthine in the urine.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:31388277

Likely benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OpenSNP
- PubMed (2)

Hetero

CT

Gene: XDH
Variant: c.627G>A
(p.Glu209=)
rsID: rs45575032
Ref Allele: C
Alt Allele: T
Freq: 2.4616%uncommon
CADD: 15.08

ClinVar Submissions (1)

- Xanthinuria

  ### Xanthinuria

  An increased concentration of xanthine in the urine.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:31387835

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CT

Gene: GALNT3
Variant: c.-295T>A
rsID: rs111425435
Ref Allele: A
Alt Allele: T
Freq: 2.4704%uncommon
CADD: 18.99

ClinVar Submissions (1)

- Tumoral calcinosis, familial, hyperphosphatemic, Autosomal recessive

  ### Tumoral calcinosis, familial, hyperphosphatemic

  Hyperphosphatemic familial tumoral calcinosis (HFTC) is characterized by: Ectopic calcifications (tumoral calcinosis) typically found in periarticular soft tissues exposed to repetitive trauma or prolonged pressure (e.g., hips, elbows, and shoulders); and Painful swellings (referred to as hyperostosis) in the areas overlying the diaphyses of the tibiae (and less often the ulna, metacarpal bones, and radius). The dental phenotype unique to HFTC includes enamel hypoplasia, short and bulbous roots, obliteration of pulp chambers and canals, and pulp stones. Less common are large and small vessel calcifications that are often asymptomatic incidental findings on radiologic studies but can also cause peripheral vascular insufficiency (e.g., pain, cold extremities, and decreased peripheral pulses). Less frequently reported findings include testicular microlithiasis and angioid streaks of the retina.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:165794201

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

AT

Gene: SH3TC2
Variant: c.*19406A>T
rsID: rs72835351
Ref Allele: T
Alt Allele: A
Freq: 2.4704%uncommon
CADD: 1.434

ClinVar Submissions (1)

- Charcot-Marie-Tooth disease type 4

  ### Charcot-Marie-Tooth disease type 4

  Charcot-Marie-Tooth disease type 4 (CMT4) belongs to the genetically heterogeneous group of CMT peripheral sensorimotor polyneuropathy diseases. Type 4 is less common and often limited to certain ethnic groups. Patients present with the typical CMT phenotype along with typical features of progressive, distally accentuated weakness and atrophy of muscles innervated by the peroneal nerve in the lower limbs, followed by weakness and atrophy of hands, sensory loss, and characteristic foot abnormalities.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 5:148985305

- Mononeuropathy of the Median Nerve

  ### Mononeuropathy of the Median Nerve

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 5:148985305

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

TA

Gene: ATN1
Variant: c.1647G>A
(p.Leu549=)
rsID: rs11547602
Ref Allele: G
Alt Allele: A
Freq: 2.4919%uncommon
CADD: 14.15

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 12:6936914

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: ACADSB
Variant: c.-123G>A
rsID: rs72839755
Ref Allele: G
Alt Allele: A
Freq: 2.499%uncommon
CADD: 9.942

ClinVar Submissions (1)

- Deficiency of 2-methylbutyryl-CoA dehydrogenase, Autosomal recessive

  ### Deficiency of 2-methylbutyryl-CoA dehydrogenase

  2-Methylbutyryl-CoA dehydrogenase (MBD) deficiency is an autosomal recessive metabolic disorder of impaired isoleucine degradation. It is most often ascertained via newborn screening and is usually clinically asymptomatic, although some patients have been reported to have delayed development and neurologic signs. Therefore, the clinical relevance of the deficiency is unclear (Sass et al.., 2008).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 10:123008907

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GA

Gene: BRCA2
Variant: c.316+1403T>C
rsID: rs11571592
Ref Allele: T
Alt Allele: C
Freq: 2.4998%uncommon
CADD: 6.143

ClinVar Submissions (1)

- Breast-ovarian cancer, familial 2, Autosomal dominant

  ### Breast-ovarian cancer, familial 2

  BRCA1- and BRCA2-associated hereditary breast and ovarian cancer syndrome (HBOC) is characterized by an increased risk for female and male breast cancer, ovarian cancer (includes fallopian tube and primary peritoneal cancers), and to a lesser extent other cancers such as prostate cancer, pancreatic cancer, and melanoma primarily in individuals with a BRCA2 pathogenic variant. The exact cancer risks differ slightly depending on whether HBOC is caused by a BRCA1 or BRCA2 pathogenic variant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 12, 2015
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 13:32320728

Expert Reviewed Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

TC

Gene: RUNX1
Variant: c.*919A>G
rsID: rs8131520
Ref Allele: T
Alt Allele: C
Freq: 2.519%uncommon
CADD: 3.086

ClinVar Submissions (1)

- Familial platelet disorder with associated myeloid malignancy, Autosomal dominant

  ### Familial platelet disorder with associated myeloid malignancy

  Disease that is characterised by moderate thrombocytopenia, abnormal platelet function and the propensity to develop myeloid malignancies, in particular acute myelogenous leukaemia. The prevalence is unknown but the disease has been reported in less than 20 families. Causative mutations have been identified in the RUNX1 gene (also known as AML1 or CBFA2; chromosome 21q22.3) in most of the analysed families. The condition is inherited as an autosomal dominant trait.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 21:34791216

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

TC

Gene: DEPDC5
Variant: c.1095T>C
(p.Asp365=)
rsID: rs79070552
Ref Allele: T
Alt Allele: C
Freq: 2.5206%uncommon
CADD: 10.03

ClinVar Submissions (4)

- Epilepsy, familial focal, with variable foci 1, Autosomal dominant

  ### Epilepsy, familial focal, with variable foci 1

  DEPDC5-related epilepsy encompasses a range of epilepsy syndromes, almost all of which are characterized by focal seizures, with seizure onset in a discrete area of the brain. While most individuals with DEPDC5-related epilepsy have a normal brain MRI, some have epilepsy associated with a cortical malformation, usually focal cortical dysplasia. Seizure syndromes include familial focal epilepsy with variable foci (FFEVF), autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), familial mesial temporal lobe epilepsies (FMTLE), autosomal dominant epilepsy with auditory features (ADEAF), and infantile spasms. Although psychomotor development is usually normal, intellectual disability or autism spectrum disorder has been reported in some individuals.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 05, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 22:31804175

- Seizures

  ### Seizures

  Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or "seizure disorder."

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 05, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 22:31804175

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 05, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 22:31804175

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 05, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 22:31804175

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

TC

Gene: OTC
Variant: c.867+35T>G
rsID: rs62622415
Ref Allele: T
Alt Allele: G
Freq: 2.5436%uncommon

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: X:38409060

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Homo

GG

Gene: PMS2
Variant: c.251-72A>G
rsID: rs117831773
Ref Allele: T
Alt Allele: C
Freq: 2.5548%uncommon
CADD: 2.882

ClinVar Submissions (1)

- Lynch syndrome

  ### Lynch syndrome

  Lynch syndrome is characterized by an increased risk for colorectal cancer (CRC) and cancers of the endometrium, stomach, ovary, small bowel, hepatobiliary tract, urinary tract, brain, and skin. In individuals with Lynch syndrome the following lifetime risks for cancer are seen: CRC: 52%-82% (mean age at diagnosis 44-61 years). Endometrial cancer in females: 25%-60% (mean age at diagnosis 48-62 years). Gastric cancer: 6%-13% (mean age at diagnosis 56 years). Ovarian cancer: 4%-12% (mean age at diagnosis 42.5 years; ~30% are diagnosed < age 40 years). The risk for other Lynch syndrome-related cancers is lower, though substantially increased over general population rates.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 05, 2013
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 7:6003864

Expert Reviewed Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

TC

Gene: TRPM1
Variant: c.4135C>A
(p.Pro1379Thr)
rsID: rs61734298
Ref Allele: G
Alt Allele: T
Freq: 2.5699%uncommon
CADD: 12.95

ClinVar Submissions (1)

- Congenital Stationary Night Blindness, Recessive

  ### Congenital Stationary Night Blindness, Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 15:31002499

Likely benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OpenSNP
- PubMed (1)

Hetero

GT

Gene: CHRND
Variant: c.*1025A>G
rsID: rs115132742
Ref Allele: A
Alt Allele: G
Freq: 2.5763%uncommon
CADD: 2.174

ClinVar Submissions (1)

- Congenital Myasthenic Syndrome, Dominant/Recessive

  ### Congenital Myasthenic Syndrome, Dominant/Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:232536337

- Multiple pterygium syndrome Escobar type, Autosomal recessive

  ### Multiple pterygium syndrome Escobar type

  Multiple pterygium syndromes comprise a group of multiple congenital anomaly disorders characterized by webbing (pterygia) of the neck, elbows, and/or knees and joint contractures (arthrogryposis) (Morgan et al., 2006). The multiple pterygium syndromes are phenotypically and genetically heterogeneous but are traditionally divided into prenatally lethal (253290) and nonlethal (Escobar) types.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:232536337

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

AG

Gene: B4GALNT1
Variant: c.514G>C
(p.Gly172Arg)
rsID: rs810205
Ref Allele: C
Alt Allele: G
Freq: 2.5882%uncommon
CADD: 15.28

ClinVar Submissions (2)

- Spastic paraplegia

  ### Spastic paraplegia

  Spasticity and weakness of the leg and hip muscles.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 28, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 12:57630495

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 28, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 12:57630495

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CG

Gene: EYA4
Variant: c.*2302G>A
rsID: rs41286208
Ref Allele: G
Alt Allele: A
Freq: 2.5898%uncommon
CADD: 6.377

ClinVar Submissions (1)

- Dilated Cardiomyopathy, Dominant

  ### Dilated Cardiomyopathy, Dominant

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 6:133531107

- Nonsyndromic Hearing Loss, Dominant

  ### Nonsyndromic Hearing Loss, Dominant

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 6:133531107

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: PIEZO1
Variant: c.6390G>A
(p.Thr2130=)
rsID: rs34679131
Ref Allele: C
Alt Allele: T
Freq: 2.64%uncommon
CADD: 0.485

ClinVar Submissions (1)

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 29, 2018
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 16:88719655

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CT

Gene: HMCN1
Variant: c.*937A>G
rsID: rs41317509
Ref Allele: A
Alt Allele: G
Freq: 2.6543%uncommon
CADD: 16.36

ClinVar Submissions (1)

- Macular degeneration

  ### Macular degeneration

  A nonspecific term denoting degeneration of the retinal pigment epithelium and/or retinal photoreceptor cells of the macula lutea.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:186190815

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

AG

Gene: ADAMTS13
Variant: c.3097G>A
(p.Ala1033Thr)
rsID: rs28503257
Ref Allele: G
Alt Allele: A
Freq: 2.6575%uncommon
CADD: 24.9

ClinVar Submissions (2)

- Upshaw-Schulman syndrome, Autosomal recessive

  ### Upshaw-Schulman syndrome

  The classic pentad of TTP includes hemolytic anemia with fragmentation of erythrocytes, thrombocytopenia, diffuse and nonfocal neurologic findings, decreased renal function, and fever. Congenital TTP, also known as Schulman-Upshaw syndrome, is characterized by neonatal onset, response to fresh plasma infusion, and frequent relapses (Savasan et al., 2003; Kokame et al., 2002). Acquired TTP, which is usually sporadic, usually occurs in adults and is caused by an IgG inhibitor against the von Willebrand factor-cleaving protease.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 9:133454467

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 9:133454467

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (2)

Hetero

GA

Gene: EPAS1
Variant: c.1035-15T>C
rsID: rs116510029
Ref Allele: T
Alt Allele: C
Freq: 2.6599%uncommon
CADD: 7.618

ClinVar Submissions (1)

- Familial erythrocytosis

  ### Familial erythrocytosis

  Polycythemia that occurs in groups of related individuals.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:46376524

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

TC

Gene: BRCA1
Variant: c.5075-1584T>G
rsID: rs8176243
Ref Allele: A
Alt Allele: C
Freq: 2.6671%uncommon
CADD: 0.784

ClinVar Submissions (1)

- Breast-ovarian cancer, familial 1, Autosomal dominant

  ### Breast-ovarian cancer, familial 1

  BRCA1- and BRCA2-associated hereditary breast and ovarian cancer syndrome (HBOC) is characterized by an increased risk for female and male breast cancer, ovarian cancer (includes fallopian tube and primary peritoneal cancers), and to a lesser extent other cancers such as prostate cancer, pancreatic cancer, and melanoma primarily in individuals with a BRCA2 pathogenic variant. The exact cancer risks differ slightly depending on whether HBOC is caused by a BRCA1 or BRCA2 pathogenic variant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 12, 2015
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 17:43065535

Expert Reviewed Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

AC

Gene: CDHR1
Variant: c.159C>A
(p.His53Gln)
rsID: rs12781048
Ref Allele: C
Alt Allele: A
Freq: 2.6679%uncommon
CADD: 0.003

ClinVar Submissions (1)

- Cone-Rod Dystrophy, Recessive

  ### Cone-Rod Dystrophy, Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 10:84196512

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OpenSNP
- PubMed

Hetero

CA

Gene: FAM20C
Variant: c.1218T>A
(p.Pro406=)
rsID: rs144007479
Ref Allele: T
Alt Allele: A
Freq: 2.6743%uncommon
CADD: 6.051

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 21, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 7:255994

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

TA

Gene: GNPTAB
Variant: c.3602+8C>A
rsID: rs79493678
Ref Allele: G
Alt Allele: T
Freq: 2.6989%uncommon
CADD: 0.892

ClinVar Submissions (5)

- Mucolipidosis, Type II

  ### Mucolipidosis, Type II

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 01, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 12:101753364

- Mucolipidosis, Type III Alpha/Beta

  ### Mucolipidosis, Type III Alpha/Beta

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 01, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 12:101753364

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 01, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 12:101753364

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 01, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 12:101753364

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (2)

Hetero

GT

Gene: EPAS1
Variant: c.1908T>C
(p.Asn636=)
rsID: rs35606117
Ref Allele: T
Alt Allele: C
Freq: 2.7069%uncommon
CADD: 9.243

ClinVar Submissions (1)

- Familial erythrocytosis

  ### Familial erythrocytosis

  Polycythemia that occurs in groups of related individuals.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:46380580

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

TC

Gene: ADAMTS13
Variant: c.2910C>T
(p.Val970=)
rsID: rs28641026
Ref Allele: C
Alt Allele: T
Freq: 2.7117%uncommon
CADD: 0.366

ClinVar Submissions (2)

- Upshaw-Schulman syndrome, Autosomal recessive

  ### Upshaw-Schulman syndrome

  The classic pentad of TTP includes hemolytic anemia with fragmentation of erythrocytes, thrombocytopenia, diffuse and nonfocal neurologic findings, decreased renal function, and fever. Congenital TTP, also known as Schulman-Upshaw syndrome, is characterized by neonatal onset, response to fresh plasma infusion, and frequent relapses (Savasan et al., 2003; Kokame et al., 2002). Acquired TTP, which is usually sporadic, usually occurs in adults and is caused by an IgG inhibitor against the von Willebrand factor-cleaving protease.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 9:133449831

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 9:133449831

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (2)

Hetero

CT

Gene: SLC13A5
Variant: c.369-14C>T
rsID: rs218677
Ref Allele: G
Alt Allele: A
Freq: 2.7141%uncommon
CADD: 12.09

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 18, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 17:6704070

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: FDX2
Variant: c.210-14C>T
rsID: rs55651720
Ref Allele: G
Alt Allele: A
Freq: 2.7316%uncommon
CADD: 5.604

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 07, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 19:10315506

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: FDX2
Variant: c.154+4C>T
rsID: rs79442975
Ref Allele: G
Alt Allele: A
Freq: 2.7324%uncommon
CADD: 14.85

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 10, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 19:10315848

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: FDX2
Variant: c.85A>G
(p.Arg29Gly)
rsID: rs62640397
Ref Allele: T
Alt Allele: C
Freq: 2.7324%uncommon
CADD: 13.09

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 10, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 19:10315921

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

TC

Gene: COL18A1
Variant: c.1455G>T
(p.Val485=)
rsID: rs17338853
Ref Allele: G
Alt Allele: T
Freq: 2.7746%uncommon
CADD: 3.082

ClinVar Submissions (2)

- Knobloch syndrome 1, Autosomal recessive

  ### Knobloch syndrome 1

  Knobloch syndrome is an autosomal recessive developmental disorder primarily characterized by typical eye abnormalities, including high myopia, cataracts, dislocated lens, vitreoretinal degeneration, and retinal detachment, with occipital skull defects, which can range from occipital encephalocele to occult cutis aplasia (summary by Aldahmesh et al., 2011).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 21:45476467

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 21:45476467

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

GT

Gene: XDH
Variant: c.837C>T
(p.Val279=)
rsID: rs4407290
Ref Allele: G
Alt Allele: A
Freq: 2.7754%uncommon
CADD: 14.11

ClinVar Submissions (1)

- Xanthinuria

  ### Xanthinuria

  An increased concentration of xanthine in the urine.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:31383804

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: GFI1
Variant: c.*574G>T
rsID: rs41296171
Ref Allele: C
Alt Allele: A
Freq: 2.7937%uncommon
CADD: 9.826

ClinVar Submissions (1)

- Severe congenital neutropenia

  ### Severe congenital neutropenia

  Severe congenital neutropenia is a condition that causes affected individuals to be prone to recurrent infections. People with this condition have a shortage (deficiency) of neutrophils, a type of white blood cell that plays a role in inflammation and in fighting infection. The deficiency of neutrophils, called neutropenia, is apparent at birth or soon afterward. It leads to recurrent infections beginning in infancy, including infections of the sinuses, lungs, and liver. Affected individuals can also develop fevers and inflammation of the gums (gingivitis) and skin. Approximately 40 percent of affected people have decreased bone density (osteopenia) and may develop osteoporosis, a condition that makes bones progressively more brittle and prone to fracture. In people with severe congenital neutropenia, these bone disorders can begin at any time from infancy through adulthood.Approximately 20 percent of people with severe congenital neutropenia develop certain cancerous conditions of the blood, particularly myelodysplastic syndrome or leukemia during adolescence.Some people with severe congenital neutropenia have additional health problems such as seizures, developmental delay, or heart and genital abnormalities.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 1:92475455

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CA

Gene: LRP4
Variant: c.1501A>C
(p.Asn501His)
rsID: rs72897663
Ref Allele: T
Alt Allele: G
Freq: 2.7985%uncommon
CADD: 23

ClinVar Submissions (2)

- Myasthenic syndrome, congenital, 17, Autosomal recessive

  ### Myasthenic syndrome, congenital, 17

  Congenital myasthenic syndromes (designated as CMS throughout this entry) are characterized by fatigable weakness of skeletal muscle (e.g., ocular, bulbar, limb muscles) with onset at or shortly after birth or in early childhood; rarely, symptoms may not manifest until later in childhood. Cardiac and smooth muscle are usually not involved. Severity and course of disease are highly variable, ranging from minor symptoms to progressive disabling weakness. In some subtypes of CMS, myasthenic symptoms may be mild, but sudden severe exacerbations of weakness or even sudden episodes of respiratory insufficiency may be precipitated by fever, infections, or excitement. Major findings of the neonatal-onset subtype include: respiratory insufficiency with sudden apnea and cyanosis; feeding difficulties; poor suck and cry; choking spells; eyelid ptosis; and facial, bulbar, and generalized weakness. Arthrogryposis multiplex congenita may also be present. Stridor in infancy may be an important clue to CMS. Later childhood-onset subtypes show abnormal muscle fatigability with difficulty in activities such as running or climbing stairs; motor milestones may be delayed; fluctuating eyelid ptosis and fixed or fluctuating extraocular muscle weakness are common presentations.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:46894628

- Sclerosteosis 2, Autosomal dominant

  ### Sclerosteosis 2

  Sclerosteosis is a severe sclerosing bone dysplasia characterized by progressive skeletal overgrowth. Syndactyly is a variable manifestation. The disorder is rare and the majority of affected individuals have been reported in the Afrikaner population of South Africa (summary by Brunkow et al., 2001). For a discussion of genetic heterogeneity of sclerosteosis, see SOST1 (269500).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:46894628

- Syndactyly Cenani Lenz type, Autosomal recessive

  ### Syndactyly Cenani Lenz type

  A congenital malformation syndrome that associates a complex syndactyly of the hands with malformations of the forearm bones and similar manifestations in the lower limbs. Fewer than 30 cases have been described, the majority of cases occurred in related families. The syndrome affects both the upper and lower limbs but, in general, the latter are less severely affected. Associated malformations (renal hypoplasia and vertebral and hemi-vertebral anomalies) have occasionally been reported. Mild facial dysmorphism has been described in isolated cases. The disease is transmitted as an autosomal recessive trait. Homozygous or compound heterozygous mutations of the LRP4 gene (11p12-p11.2) have been identified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:46894628

- Syndactyly Cenani Lenz type, Autosomal recessive

  ### Syndactyly Cenani Lenz type

  A congenital malformation syndrome that associates a complex syndactyly of the hands with malformations of the forearm bones and similar manifestations in the lower limbs. Fewer than 30 cases have been described, the majority of cases occurred in related families. The syndrome affects both the upper and lower limbs but, in general, the latter are less severely affected. Associated malformations (renal hypoplasia and vertebral and hemi-vertebral anomalies) have occasionally been reported. Mild facial dysmorphism has been described in isolated cases. The disease is transmitted as an autosomal recessive trait. Homozygous or compound heterozygous mutations of the LRP4 gene (11p12-p11.2) have been identified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:46894628

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

TG

Gene: ABL1
Variant: c.2972C>T
(p.Ser991Leu)
rsID: rs2229067
Ref Allele: C
Alt Allele: T
Freq: 2.8065%uncommon
CADD: 6.648

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 19, 2013
  Review Status: no assertion provided
  Number of Submitters: 1
  Clinical Significance: not provided
  Assembly: GRCh38
  Chromosome/Position: 9:130885205

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: UGT2A1
Variant: c.576T>A
(p.Tyr192Ter)
rsID: rs111696697
Ref Allele: A
Alt Allele: T
Freq: 2.8773%uncommon
CADD: 36

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 28, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 4:69647069

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

AT

Gene: NDUFAF1
Variant: c.-386A>T
rsID: rs111326645
Ref Allele: T
Alt Allele: A
Freq: 2.8781%uncommon
CADD: 8.888

ClinVar Submissions (1)

- Mitochondrial complex I deficiency

  ### Mitochondrial complex I deficiency

  Isolated complex I deficiency is the most common enzymatic defect of the oxidative phosphorylation disorders (McFarland et al., 2004; Kirby et al., 2004). It causes a wide range of clinical disorders, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, nonspecific encephalopathy, hypertrophic cardiomyopathy, myopathy, liver disease, Leigh syndrome (see 256000), Leber hereditary optic neuropathy (535000), and some forms of Parkinson disease (see 556500) (Loeffen et al., 2000; Pitkanen et al., 1996; Robinson, 1998). Genetic Heterogeneity of Complex I Deficiency Mitochondrial complex I deficiency shows extreme genetic heterogeneity and can be caused by mutation in nuclear-encoded genes or in mitochondrial-encoded genes. There are no obvious genotype-phenotype correlations, and inference of the underlying basis from the clinical or biochemical presentation is difficult, if not impossible (summary by Haack et al., 2012). However, the majority of cases are caused by mutations in nuclear-encoded genes (Loeffen et al., 2000; Triepels et al., 2001). Complex I deficiency resulting from mutation in nuclear-encoded genes include MC1DN1, caused by mutation in the NDUFS4 gene (602694); MC1DN2 (618222), caused by mutation in the NDUFS8 gene (602141); MC1DN3 (618224), caused by mutation in the NDUFS7 gene (601825); MC1DN4 (618225), caused by mutation in the NDUFV1 gene (161015); MC1DN5 (618226), caused by mutation in the NDUFS1 gene (157655); MC1DN6 (618228), caused by mutation in the NDUFS2 gene (602985); MC1DN7 (618229), caused by mutation in the NDUFV2 gene (600532); MC1DN8 (618230), caused by mutation in the NDUFS3 gene (603846); MC1DN9 (618232), caused by mutation in the NDUFS6 gene (603848); MC1DN10 (618233), caused by mutation in the NDUFAF2 gene (609653); MC1DN11 (618234), caused by mutation in the NDUFAF1 gene (606934); MC1DN12 (301020), caused by mutation in the NDUFA1 gene (300078); MC1DN13 (618235), caused by mutation in the NDUFA2 gene (602137); MC1DN14 (618236), caused by mutation in the NDUFA11 gene (612638); MC1DN15 (618237), caused by mutation in the NDUFAF4 gene (611776); MC1DN16 (618238), caused by mutation in the NDUFAF5 gene (612360); MC1DN17 (618239), caused by mutation in the NDUFAF6 gene (612392); MC1DN18 (618240), caused by mutation in the NDUFAF3 gene (612911); MC1DN19 (618241), caused by mutation in the FOXRED1 gene (613622); MC1DN20 (611126), caused by mutation in the ACAD9 gene (611103); MC1DN21 (618242), caused by mutation in the NUBPL gene (613621); MC1DN22 (618243), caused by mutation in the NDUFA10 gene (603835); MC1DN23 (618244), caused by mutation in the NDUFA12 gene (614530); MC1DN24 (618245), caused by mutation in the NDUFB9 gene (601445); MC1DN25 (618246), caused by mutation in the NDUFB3 gene (603839); MC1DN26 (618247), caused by mutation in the NDUFA9 gene (603834); MC1DN27 (618248), caused by mutation in the MTFMT gene (611766); MC1DN28 (618249), caused by mutation in the NDUFA13 gene (609435); MC1DN29 (618250), caused by mutation in the TMEM126B gene (615533); MC1DN30 (301021), caused by mutation in the NDUFB11 gene (300403); MC1DN31 (618251), caused by mutation in the TIMMDC1 gene (615534); MC1DN32 (618252), caused by mutation in the NDUFB8 gene (602140); and MC1DN33 (618253), caused by mutation in the NDUFA6 gene (602138). Complex I deficiency with mitochondrial inheritance has been associated with mutation in 6 mitochondrial-encoded components of complex I: MTND1 (516000), MTND2 (516001), MTND3 (516002), MTND4 (516003), MTND5 (516005), MTND6 (516006). Most of these patients have a phenotype of Leber hereditary optic neuropathy (LHON; 535000) or Leigh syndrome. Features of complex I deficiency may also be caused by mutation in other mitochondrial genes, including MTTS2 (590085).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 15:41402448

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

TA

Gene: SYCP3
Variant: c.-118T>A
rsID: rs17031944
Ref Allele: A
Alt Allele: T
Freq: 2.8885%uncommon
CADD: 6.276

ClinVar Submissions (1)

- Spermatogenic Failure

  ### Spermatogenic Failure

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 12:101739455

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

AT

Gene: GNPTAB
Variant: c.204-15G>T
rsID: rs10860787
Ref Allele: C
Alt Allele: A
Freq: 2.8925%uncommon
CADD: 0.534

ClinVar Submissions (3)

- Mucolipidosis, Type II

  ### Mucolipidosis, Type II

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 06, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 12:101790072

- Mucolipidosis, Type III Alpha/Beta

  ### Mucolipidosis, Type III Alpha/Beta

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 06, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 12:101790072

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 06, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 12:101790072

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CA

Gene: SHARPIN
Variant: c.880C>T
(p.Pro294Ser)
rsID: rs34674752
Ref Allele: G
Alt Allele: A
Freq: 2.9084%uncommon
CADD: 18.02

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 29, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 8:144099319

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: GUCY2D
Variant: c.3044-7G>T
rsID: rs56348143
Ref Allele: G
Alt Allele: T
Freq: 2.9156%uncommon
CADD: 6.284

ClinVar Submissions (2)

- Cone-rod dystrophy 6, Autosomal dominant

  ### Cone-rod dystrophy 6

  Cone-rod dystrophy is a group of related eye disorders that causes vision loss, which becomes more severe over time. These disorders affect the retina, which is the layer of light-sensitive tissue at the back of the eye. In people with cone-rod dystrophy, vision loss occurs as the light-sensing cells of the retina gradually deteriorate.The first signs and symptoms of cone-rod dystrophy, which often occur in childhood, are usually decreased sharpness of vision (visual acuity) and increased sensitivity to light (photophobia). These features are typically followed by impaired color vision (dyschromatopsia), blind spots (scotomas) in the center of the visual field, and partial side (peripheral) vision loss. Over time, affected individuals develop night blindness and a worsening of their peripheral vision, which can limit independent mobility. Decreasing visual acuity makes reading increasingly difficult and most affected individuals are legally blind by mid-adulthood. As the condition progresses, individuals may develop involuntary eye movements (nystagmus).There are more than 30 types of cone-rod dystrophy, which are distinguished by their genetic cause and their pattern of inheritance: autosomal recessive, autosomal dominant, and X-linked. Additionally, cone-rod dystrophy can occur alone without any other signs and symptoms or it can occur as part of a syndrome that affects multiple parts of the body.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 09, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 17:8015920

- Leber congenital amaurosis 1, Autosomal recessive

  ### Leber congenital amaurosis 1

  Leber congenital amaurosis is an eye disorder that primarily affects the retina, which is the specialized tissue at the back of the eye that detects light and color. People with this disorder typically have severe visual impairment beginning in infancy. The visual impairment tends to be stable, although it may worsen very slowly over time.Leber congenital amaurosis is also associated with other vision problems, including an increased sensitivity to light (photophobia), involuntary movements of the eyes (nystagmus), and extreme farsightedness (hyperopia). The pupils, which usually expand and contract in response to the amount of light entering the eye, do not react normally to light. Instead, they expand and contract more slowly than normal, or they may not respond to light at all. Additionally, the clear front covering of the eye (the cornea) may be cone-shaped and abnormally thin, a condition known as keratoconus.A specific behavior called Franceschetti's oculo-digital sign is characteristic of Leber congenital amaurosis. This sign consists of poking, pressing, and rubbing the eyes with a knuckle or finger. Researchers suspect that this behavior may contribute to deep-set eyes and keratoconus in affected children.In rare cases, delayed development and intellectual disability have been reported in people with the features of Leber congenital amaurosis. However, researchers are uncertain whether these individuals actually have Leber congenital amaurosis or another syndrome with similar signs and symptoms.At least 13 types of Leber congenital amaurosis have been described. The types are distinguished by their genetic cause, patterns of vision loss, and related eye abnormalities.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 09, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 17:8015920

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 09, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 17:8015920

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

GT

Gene: SACS
Variant: c.-531G>A
rsID: rs73154650
Ref Allele: C
Alt Allele: T
Freq: 2.9299%uncommon
CADD: 10.98

ClinVar Submissions (1)

- Spastic ataxia Charlevoix-Saguenay type, Autosomal recessive

  ### Spastic ataxia Charlevoix-Saguenay type

  ARSACS (autosomal recessive spastic ataxia of Charlevoix-Saguenay) is characterized in individuals born in Quebec Province by early-onset (age 12-18 months) difficulty in walking and gait unsteadiness. In individuals with ARSACS born outside the Province of Quebec, onset is often delayed until later childhood and even adulthood. Ataxia, dysarthria, spasticity, extensor plantar reflexes, distal muscle wasting, a distal sensorimotor neuropathy predominant in the legs, and horizontal gaze-evoked nystagmus constitute the most frequent progressive neurologic signs. Increased demarcation of the retinal nerve fibers located near the vessels close to the optic disc (formerly designated as yellow streaks of hypermyelinated fibers) is very common in individuals with ARSACS who originate from Quebec but may be absent in non-Quebec born individuals. Individuals with ARSACS born in the Province of Quebec become wheelchair bound at the average age of 41 years; cognitive skills are preserved in the long term as individuals remain able to perform daily living tasks late into adulthood. Death commonly occurs in the sixth decade.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 13:23433644

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CT

Gene: PLCG2
Variant: c.2054+7G>A
rsID: rs138158454
Ref Allele: G
Alt Allele: A
Freq: 2.9506%uncommon
CADD: 2.985

ClinVar Submissions (1)

- Familial cold autoinflammatory syndrome 3, Autosomal dominant

  ### Familial cold autoinflammatory syndrome 3

  Familial cold autoinflammatory syndrome-2 is an autosomal dominant immune disorder characterized by the development of cutaneous urticaria, erythema, and pruritus in response to cold exposure. Affected individuals have variable additional immunologic defects, including antibody deficiency, decreased numbers of B cells, defective B cells, increased susceptibility to infection, and increased risk of autoimmune disorders (summary by Ombrello et al., 2012). For a discussion of genetic heterogeneity of FCAS, see FCAS1 (120100).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 21, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 16:81912723

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GA

Gene: DIAPH1
Variant: c.*1347C>G
rsID: rs251020
Ref Allele: G
Alt Allele: C
Freq: 2.953%uncommon
CADD: 9.03

ClinVar Submissions (1)

- Nonsyndromic Hearing Loss, Mixed

  ### Nonsyndromic Hearing Loss, Mixed

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:141515504

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GC

Gene: RNASEH2C
Variant: c.*1776C>T
rsID: rs4645936
Ref Allele: G
Alt Allele: A
Freq: 2.9817%uncommon
CADD: 1.173

ClinVar Submissions (1)

- Aicardi Goutieres syndrome

  ### Aicardi Goutieres syndrome

  Most characteristically, Aicardi-Goutières syndrome (AGS) manifests as an early-onset encephalopathy that usually, but not always, results in severe intellectual and physical disability. A subgroup of infants with AGS present at birth with abnormal neurologic findings, hepatosplenomegaly, elevated liver enzymes, and thrombocytopenia, a picture highly suggestive of congenital infection. Otherwise, most affected infants present at variable times after the first few weeks of life, frequently after a period of apparently normal development. Typically, they demonstrate the subacute onset of a severe encephalopathy characterized by extreme irritability, intermittent sterile pyrexias, loss of skills, and slowing of head growth. Over time, as many as 40% develop chilblain skin lesions on the fingers, toes, and ears. It is becoming apparent that atypical, sometimes milder, cases of AGS exist, and thus the true extent of the phenotype associated with pathogenic variants in the AGS-related genes is not yet known.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:65718007

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: EPCAM
Variant: c.904-12T>C
rsID: rs62139669
Ref Allele: T
Alt Allele: C
Freq: 2.9952%uncommon
CADD: 6.584

ClinVar Submissions (3)

- Lynch syndrome

  ### Lynch syndrome

  Lynch syndrome is characterized by an increased risk for colorectal cancer (CRC) and cancers of the endometrium, stomach, ovary, small bowel, hepatobiliary tract, urinary tract, brain, and skin. In individuals with Lynch syndrome the following lifetime risks for cancer are seen: CRC: 52%-82% (mean age at diagnosis 44-61 years). Endometrial cancer in females: 25%-60% (mean age at diagnosis 48-62 years). Gastric cancer: 6%-13% (mean age at diagnosis 56 years). Ovarian cancer: 4%-12% (mean age at diagnosis 42.5 years; ~30% are diagnosed < age 40 years). The risk for other Lynch syndrome-related cancers is lower, though substantially increased over general population rates.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:47386560

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:47386560

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (2)

Hetero

TC

Gene: MYO1C
Variant: c.1377+9T>G
rsID: rs2286877
Ref Allele: A
Alt Allele: C
Freq: 3.0462%uncommon
CADD: 10.84

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 22, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 17:1477882

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

AC

Gene: LMBR1
Variant: c.357T>C
(p.Cys119=)
rsID: rs112583005
Ref Allele: A
Alt Allele: G
Freq: 3.0525%uncommon
CADD: 13.73

ClinVar Submissions (1)

- Triphalangeal thumb polysyndactyly syndrome

  ### Triphalangeal thumb polysyndactyly syndrome

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 7:156796455

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

AG

Gene: CCDC50
Variant: c.363A>T
(p.Leu121Phe)
rsID: rs35380043
Ref Allele: A
Alt Allele: T
Freq: 3.0669%uncommon
CADD: 24

ClinVar Submissions (3)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 29, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 3:191369951

Benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OpenSNP
- PubMed (2)

Hetero

AT

Gene: TMC8
Variant: c.1665-5G>T
rsID: rs11651864
Ref Allele: G
Alt Allele: T
Freq: 3.0685%uncommon
CADD: 6.376

ClinVar Submissions (1)

- EPIDERMODYSPLASIA VERRUCIFORMIS, Autosomal recessive

  ### EPIDERMODYSPLASIA VERRUCIFORMIS

  Epidermodysplasia verruciformis (EV) is a rare genodermatosis associated with a high risk of skin cancer. EV results from an abnormal susceptibility to specific related human papillomavirus (HPV) genotypes and to the oncogenic potential of some of them, mainly HPV5. Infection with EV-associated HPV leads to the early development of disseminated flat wart-like and pityriasis versicolor-like lesions. Patients are unable to reject their lesions, and cutaneous Bowen carcinomas in situ and invasive squamous cell carcinomas develop in about half of them, mainly on sun-exposed areas (summary by Ramoz et al., 2000). Genetic Heterogeneity of Susceptibility to Epidermodysplasia Verruciformis Susceptibility to EV2 (618231) is conferred by mutation in the TMC8 gene (605829) on chromosome 17q25; EV3 (618267) by mutation in the CIB1 gene (602293) on chromosome 15q26; EV4 (618307) by mutation in the RHOH gene (602037) on chromosome 4p13; and EV5 (618309) by mutation in the IL7 gene (146660) on chromosome 8q12.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 11, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 17:78138569

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GT

Gene: BCOR
Variant: c.1791C>T
(p.His597=)
rsID: rs144606152
Ref Allele: G
Alt Allele: A
Freq: 3.082%uncommon

ClinVar Submissions (4)

- History of neurodevelopmental disorder

  ### History of neurodevelopmental disorder

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 26, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: X:40073555

- Oculofaciocardiodental syndrome, X-linked dominant

  ### Oculofaciocardiodental syndrome

  Lenz microphthalmia syndrome (LMS) is characterized by unilateral or bilateral microphthalmia and/or clinical anophthalmia with malformations of the ears, teeth, fingers, skeleton, and/or genitourinary system. Microphthalmia is often accompanied by microcornea and glaucoma. Coloboma is present in approximately 60% of microphthalmic eyes with severity ranging from isolated iris coloboma to coloboma of the ciliary body, choroid, and optic disk. Ears may be low set, anteverted, posteriorly rotated, simple, cup shaped, or abnormally modeled. Hearing loss has been observed. Dental findings include irregularly shaped, missing, or widely spaced teeth. Duplicated thumbs, syndactyly, clinodactyly, camptodactyly, and microcephaly are common, as are narrow/sloping shoulders, underdeveloped clavicles, kyphoscoliosis, exaggerated lumbar lordosis, long cylindric thorax, and webbed neck. Genitourinary anomalies include hypospadias, cryptorchidism, renal hypoplasia/aplasia, and hydroureter. Approximately 60% of affected males have mild-to-severe intellectual disability or developmental delay.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 26, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: X:40073555

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 26, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: X:40073555

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (2)

Homo

AA

Gene: CHKB
Variant: c.*96G>C
rsID: rs17001634
Ref Allele: C
Alt Allele: G
Freq: 3.0924%uncommon
CADD: 8.733

ClinVar Submissions (1)

- Congenital Muscular Dystrophy, CHKB-related

  ### Congenital Muscular Dystrophy, CHKB-related

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 22:50579085

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CG

Gene: TMC8
Variant: c.1501G>A
(p.Val501Ile)
rsID: rs11651675
Ref Allele: G
Alt Allele: A
Freq: 3.0931%uncommon
CADD: 3.957

ClinVar Submissions (1)

- EPIDERMODYSPLASIA VERRUCIFORMIS, Autosomal recessive

  ### EPIDERMODYSPLASIA VERRUCIFORMIS

  Epidermodysplasia verruciformis (EV) is a rare genodermatosis associated with a high risk of skin cancer. EV results from an abnormal susceptibility to specific related human papillomavirus (HPV) genotypes and to the oncogenic potential of some of them, mainly HPV5. Infection with EV-associated HPV leads to the early development of disseminated flat wart-like and pityriasis versicolor-like lesions. Patients are unable to reject their lesions, and cutaneous Bowen carcinomas in situ and invasive squamous cell carcinomas develop in about half of them, mainly on sun-exposed areas (summary by Ramoz et al., 2000). Genetic Heterogeneity of Susceptibility to Epidermodysplasia Verruciformis Susceptibility to EV2 (618231) is conferred by mutation in the TMC8 gene (605829) on chromosome 17q25; EV3 (618267) by mutation in the CIB1 gene (602293) on chromosome 15q26; EV4 (618307) by mutation in the RHOH gene (602037) on chromosome 4p13; and EV5 (618309) by mutation in the IL7 gene (146660) on chromosome 8q12.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 11, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 17:78138156

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GA

Gene: TP63
Variant: c.1652+46G>A
rsID: rs35558939
Ref Allele: G
Alt Allele: A
Freq: 3.1178%uncommon
CADD: 1.787

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 3:189889530

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: SEMA4A
Variant: c.2138G>A
(p.Arg713Gln)
rsID: rs41265017
Ref Allele: G
Alt Allele: A
Freq: 3.1266%uncommon
CADD: 22.6

ClinVar Submissions (5)

- Cone-Rod Dystrophy, Recessive

  ### Cone-Rod Dystrophy, Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 5
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 1:156176849
  OMIM Allelic Variant: 607292.0003

- Retinitis Pigmentosa, Recessive

  ### Retinitis Pigmentosa, Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 5
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 1:156176849
  OMIM Allelic Variant: 607292.0003

- Retinitis pigmentosa 35, Autosomal dominant

  ### Retinitis pigmentosa 35

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 5
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 1:156176849
  OMIM Allelic Variant: 607292.0003

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 5
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 1:156176849
  OMIM Allelic Variant: 607292.0003

Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (5)

Hetero

GA

Gene: PIGA
Variant: c.55C>T
(p.Arg19Trp)
rsID: rs34422225
Ref Allele: G
Alt Allele: A
Freq: 3.1385%uncommon

ClinVar Submissions (4)

- History of neurodevelopmental disorder

  ### History of neurodevelopmental disorder

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 31, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: X:15331876

- Multiple congenital anomalies-hypotonia-seizures syndrome 2, X-linked recessive

  ### Multiple congenital anomalies-hypotonia-seizures syndrome 2

  Multiple congenital anomalies-hypotonia-seizures syndrome-2 is an X-linked recessive neurodevelopmental disorder characterized by dysmorphic features, neonatal hypotonia, myoclonic seizures, and variable congenital anomalies involving the central nervous, cardiac, and urinary systems. Some affected individuals die in infancy (summary by Johnston et al., 2012). The phenotype shows clinical variability with regard to severity and extraneurologic features. However, most patients present in infancy with early-onset epileptic encephalopathy associated with developmental arrest and subsequent severe neurologic disability (summary by Belet et al., 2014, Kato et al., 2014). The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis. For a discussion of genetic heterogeneity of MCAHS, see MCAHS1 (614080); for a discussion of genetic heterogeneity of EIEE, see 308350; and for a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 31, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: X:15331876

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 31, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: X:15331876

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 31, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: X:15331876

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Homo

AA

Gene: THAP1
Variant: c.*686A>G
rsID: rs11557527
Ref Allele: T
Alt Allele: C
Freq: 3.1561%uncommon
CADD: 6.297

ClinVar Submissions (1)

- Dystonia

  ### Dystonia

  An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 8:42837276

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

TC

Gene: MALT1
Variant: c.-84G>A
rsID: rs56142402
Ref Allele: G
Alt Allele: A
Freq: 3.1967%uncommon
CADD: 14.57

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 29, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 18:58671560

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: PIKFYVE
Variant: c.-160A>G
rsID: rs34366347
Ref Allele: A
Alt Allele: G
Freq: 3.2309%uncommon
CADD: 8.543

ClinVar Submissions (1)

- Fleck corneal dystrophy, Autosomal dominant

  ### Fleck corneal dystrophy

  Fleck corneal dystrophy (CFD) is a rare autosomal dominant disease characterized by numerous tiny, dot-like white flecks scattered in all layers of the corneal stroma. Typically, the stroma located in between the flecks is clear, and the endothelium, the epithelium, Bowman layer, and Descemet membrane are normal. Patients are usually asymptomatic with normal vision, yet a small number of patients report the sensation of a minor photophobia. The flecks in CFD can appear as early as 2 years of age, or sometimes even at birth, and appear not to progress significantly throughout life. Histologically, the corneal flecks appear to correspond to abnormal keratocytes swollen with membrane-limited intracytoplasmic vesicles containing complex lipids and glycosaminoglycans (summary by Kawasaki et al., 2012).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 2:208266265

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

AG

Gene: SALL1
Variant: c.*997C>A
rsID: rs116971887
Ref Allele: G
Alt Allele: T
Freq: 3.2325%uncommon
CADD: 17.33

ClinVar Submissions (1)

- Townes-Brocks syndrome 1, Autosomal dominant

  ### Townes-Brocks syndrome 1

  Townes-Brocks syndrome (TBS) is characterized by the triad of imperforate anus (84%), dysplastic ears (87%; overfolded superior helices and preauricular tags; frequently associated with sensorineural and/or conductive hearing impairment [65%]), and thumb malformations (89%; triphalangeal thumbs, duplication of the thumb [preaxial polydactyly], and rarely hypoplasia of the thumbs). Renal impairment (42%), including end-stage renal disease (ESRD), may occur with or without structural abnormalities (mild malrotation, ectopia, horseshoe kidney, renal hypoplasia, polycystic kidneys, vesicoutereral reflux). Congenital heart disease occurs in 25%. Foot malformations (52%; flat feet, overlapping toes) and genitourinary malformations (36%) are common. Intellectual disability occurs in approximately 10% of individuals. Rare features include iris coloboma, Duane anomaly, Arnold-Chiari malformation type 1, and growth retardation.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 16:51136115

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GT

Gene: SPG11
Variant: c.3420G>A
(p.Leu1140=)
rsID: rs36014111
Ref Allele: C
Alt Allele: T
Freq: 3.2389%uncommon
CADD: 8.158

ClinVar Submissions (7)

- Spastic Paraplegia, Recessive

  ### Spastic Paraplegia, Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 15:44608477

- Spastic paraplegia 11, autosomal recessive, Autosomal recessive

  ### Spastic paraplegia 11, autosomal recessive

  Spastic paraplegia 11 (SPG11) is characterized by progressive spasticity and weakness of the lower limbs frequently associated with the following: mild intellectual disability with learning difficulties in childhood and/or progressive cognitive decline; peripheral neuropathy; pseudobulbar involvement; and increased reflexes in the upper limbs. Less frequent findings include: cerebellar signs (ataxia, nystagmus, saccadic pursuit); retinal degeneration; pes cavus; scoliosis; and parkinsonism. Onset occurs mainly during infancy or adolescence (range: age 1-31 years). Most affected individuals become wheelchair bound one or two decades after disease onset.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 15:44608477

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 15:44608477

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: MYH9
Variant: c.3345A>G
(p.Glu1115=)
rsID: rs875725
Ref Allele: T
Alt Allele: C
Freq: 3.2763%uncommon
CADD: 11.07

ClinVar Submissions (4)

- MYH9-related disorder

  ### MYH9-related disorder

  An autosomal dominant disorder characterized by the triad of thrombocytopenia, giant platelets, and characteristic inclusions in peripheral blood leukocytes, without other organ dysfunction; it is associated with mutation of the MYH9 gene.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 09, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 22:36295645

- Nonsyndromic Hearing Loss, Dominant

  ### Nonsyndromic Hearing Loss, Dominant

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 09, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 22:36295645

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 09, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 22:36295645

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (5)

Hetero

TC

Gene: BMPER
Variant: c.-141+4A>G
rsID: rs113711026
Ref Allele: A
Alt Allele: G
Freq: 3.2875%uncommon
CADD: 13.03

ClinVar Submissions (1)

- Diaphanospondylodysostosis, Autosomal recessive

  ### Diaphanospondylodysostosis

  Diaphanospondylodysostosis is a rare, recessively inherited, perinatal lethal skeletal disorder. The primary skeletal characteristics include small chest, abnormal vertebral segmentation, and posterior rib gaps containing incompletely differentiated mesenchymal tissue. Consistent craniofacial features include ocular hypertelorism, epicanthal folds, depressed nasal bridge with short nose, and low-set ears. The most commonly described extraskeletal finding is nephroblastomatosis with cystic kidneys, but other visceral findings have been described in some cases (summary by Funari et al., 2010).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 7:33905148

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

AG

Gene: ECH1
Variant: c.-2C>A
rsID: rs117820732
Ref Allele: G
Alt Allele: T
Freq: 3.2986%uncommon
CADD: 6.673

ClinVar Submissions (1)

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 04, 2017
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 19:38831774

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GT

Gene: HEXA
Variant: c.1195A>G
(p.Asn399Asp)
rsID: rs1800430
Ref Allele: T
Alt Allele: C
Freq: 3.3034%uncommon
CADD: 7.897

ClinVar Submissions (7)

- Tay-Sachs disease, Autosomal recessive

  ### Tay-Sachs disease

  Hexosaminidase A deficiency results in a group of neurodegenerative disorders caused by intralysosomal storage of the specific glycosphingolipid, GM2 ganglioside. The prototype hexosaminidase A deficiency is Tay-Sachs disease, also known as the acute infantile variant. Tay-Sachs disease is characterized by progressive weakness, loss of motor skills, decreased attentiveness, and increased startle response beginning between ages three and six months with progressive evidence of neurodegeneration including: seizures, blindness, spasticity, eventual total incapacitation, and death, usually before age four years. The juvenile (subacute), chronic, and adult-onset variants of hexosaminidase A deficiency have later onsets, slower progression, and more variable neurologic findings, including: progressive dystonia, spinocerebellar degeneration, motor neuron disease, and, in some individuals with adult-onset disease, a bipolar form of psychosis.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 25, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 15:72346662

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 25, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 15:72346662

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 25, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 15:72346662

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (2)

Hetero

TC

Gene: IDUA
Variant: c.300-44C>T
rsID: rs3755956
Ref Allele: C
Alt Allele: T
Freq: 3.3145%uncommon
CADD: 1.023

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 4:1000568

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: SLC5A5
Variant: c.-70C>T
rsID: rs118133504
Ref Allele: C
Alt Allele: T
Freq: 3.3145%uncommon
CADD: 3.224

ClinVar Submissions (1)

- Thyroid Hormonogenesis Defect

  ### Thyroid Hormonogenesis Defect

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 19:17872250

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CT

Gene: PIKFYVE
Variant: c.1849A>G
(p.Met617Val)
rsID: rs16840913
Ref Allele: A
Alt Allele: G
Freq: 3.3193%uncommon
CADD: 24.3

ClinVar Submissions (1)

- Fleck corneal dystrophy, Autosomal dominant

  ### Fleck corneal dystrophy

  Fleck corneal dystrophy (CFD) is a rare autosomal dominant disease characterized by numerous tiny, dot-like white flecks scattered in all layers of the corneal stroma. Typically, the stroma located in between the flecks is clear, and the endothelium, the epithelium, Bowman layer, and Descemet membrane are normal. Patients are usually asymptomatic with normal vision, yet a small number of patients report the sensation of a minor photophobia. The flecks in CFD can appear as early as 2 years of age, or sometimes even at birth, and appear not to progress significantly throughout life. Histologically, the corneal flecks appear to correspond to abnormal keratocytes swollen with membrane-limited intracytoplasmic vesicles containing complex lipids and glycosaminoglycans (summary by Kawasaki et al., 2012).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 2:208315215

Benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed

Hetero

AG

Gene: PEX2
Variant: c.*1909G>T
rsID: rs112352942
Ref Allele: C
Alt Allele: A
Freq: 3.3313%uncommon
CADD: 0.219

ClinVar Submissions (1)

- Zellweger syndrome, Autosomal recessive

  ### Zellweger syndrome

  Zellweger spectrum disorder (ZSD) is a phenotypic continuum ranging from severe to mild. While individual phenotypes (e.g., Zellweger syndrome [ZS], neonatal adrenoleukodystrophy [NALD], and infantile Refsum disease [IRD]) were described in the past before the biochemical and molecular bases of this spectrum were fully determined, the term ZSD is now used to refer to all individuals with a PEX gene defect regardless of phenotype. Individuals with ZSD usually come to clinical attention in the newborn period or later in childhood. Affected newborns are hypotonic and feed poorly. They have distinctive facies, congenital malformations (neuronal migration defects associated with neonatal-onset seizures, renal cysts, and bony stippling [chondrodysplasia punctata] of the patella[e] and other long bones), and liver disease which can be severe. Infants with severe ZSD are significantly impaired and typically die during the first year of life, usually having made no developmental progress. Individuals with intermediate/milder ZSD do not have congenital malformations, but rather progressive peroxisome dysfunction variably manifest as sensory loss (secondary to retinal dystrophy and sensorineural hearing loss); neurologic involvement (ataxia, polyneuropathy, and leukodystrophy); liver dysfunction; adrenal insufficiency; and renal oxalate stones. While hypotonia and developmental delays are typical, intellect can be normal. Some have osteopenia; almost all have ameleogenesis imperfecta in the secondary teeth.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 8:76981352

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CA

Gene: BMPER
Variant: c.-211G>A
rsID: rs112890951
Ref Allele: G
Alt Allele: A
Freq: 3.3368%uncommon
CADD: 12.38

ClinVar Submissions (1)

- Diaphanospondylodysostosis, Autosomal recessive

  ### Diaphanospondylodysostosis

  Diaphanospondylodysostosis is a rare, recessively inherited, perinatal lethal skeletal disorder. The primary skeletal characteristics include small chest, abnormal vertebral segmentation, and posterior rib gaps containing incompletely differentiated mesenchymal tissue. Consistent craniofacial features include ocular hypertelorism, epicanthal folds, depressed nasal bridge with short nose, and low-set ears. The most commonly described extraskeletal finding is nephroblastomatosis with cystic kidneys, but other visceral findings have been described in some cases (summary by Funari et al., 2010).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 7:33905074

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GA

Gene: RYR1
Variant: c.13671C>G
(p.Ser4557=)
rsID: rs35959206
Ref Allele: C
Alt Allele: G
Freq: 3.3472%uncommon
CADD: 0.956

ClinVar Submissions (8)

- Malignant hyperthermia susceptibility

  ### Malignant hyperthermia susceptibility

  Malignant hyperthermia susceptibility (MHS) is a pharmacogenetic disorder of skeletal muscle calcium regulation associated with uncontrolled skeletal muscle hypermetabolism. Manifestations of malignant hyperthermia (MH) are precipitated by certain volatile anesthetics (i.e., halothane, isoflurane, sevoflurane, desflurane, enflurane), either alone or in conjunction with a depolarizing muscle relaxant (specifically, succinylcholine). The triggering substances release calcium stores from the sarcoplasmic reticulum and may promote entry of calcium from the myoplasm, causing contracture of skeletal muscles, glycogenolysis, and increased cellular metabolism, resulting in production of heat and excess lactate. Affected individuals experience: acidosis, hypercapnia, tachycardia, hyperthermia, muscle rigidity, compartment syndrome, rhabdomyolysis with subsequent increase in serum creatine kinase (CK) concentration, hyperkalemia with a risk for cardiac arrhythmia or even arrest, and myoglobinuria with a risk for renal failure. In nearly all cases, the first manifestations of MH (tachycardia and tachypnea) occur in the operating room; however, MH may also occur in the early postoperative period. There is mounting evidence that some affected individuals will also develop MH with exercise and/or on exposure to hot environments. Without proper and prompt treatment with dantrolene sodium, mortality is extremely high.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 29, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 8
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 19:38570618

- Multiminicore Disease

  ### Multiminicore Disease

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 29, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 8
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 19:38570618

- Myopathy, Central Core, Autosomal dominant

  ### Myopathy, Central Core

  Central core disease (CCD) is characterized by muscle weakness ranging from mild to severe. Most affected individuals have mild disease with symmetric proximal muscle weakness and variable involvement of facial and neck muscles. The extraocular muscles are often spared. Motor development is usually delayed, but in general, most affected individuals acquire independent ambulation. Life span is usually normal. Severe disease is early in onset with profound hypotonia often accompanied by poor fetal movement, spinal deformities, hip dislocation, joint contractures, poor suck, and respiratory insufficiency requiring assisted ventilation. The outcome ranges from death in infancy to survival beyond age five years. The weakness in CCD is not typically progressive.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 29, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 8
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 19:38570618

- Neuromuscular disease, congenital, with uniform type 1 fiber

  ### Neuromuscular disease, congenital, with uniform type 1 fiber

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 29, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 8
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 19:38570618

- RYR1-Related Disorders

  ### RYR1-Related Disorders

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 29, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 8
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 19:38570618

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 29, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 8
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 19:38570618

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 29, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 8
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 19:38570618

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (4)

Hetero

CG

Gene: MERTK
Variant: c.60A>T
(p.Arg20Ser)
rsID: rs35898499
Ref Allele: A
Alt Allele: T
Freq: 3.3512%uncommon
CADD: 14.81

ClinVar Submissions (3)

- Retinitis Pigmentosa, Recessive

  ### Retinitis Pigmentosa, Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:111898795

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:111898795

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:111898795

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OpenSNP
- PubMed (1)

Hetero

AT

Gene: CFTR
Variant: c.743+40A>G
rsID: rs1800502
Ref Allele: A
Alt Allele: G
Freq: 3.3528%uncommon
CADD: 0.902

ClinVar Submissions (3)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 05, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 7:117535451

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

AG

Gene: WDR62
Variant: c.3639C>T
(p.Ser1213=)
rsID: rs45470992
Ref Allele: C
Alt Allele: T
Freq: 3.3528%uncommon
CADD: 3.464

ClinVar Submissions (4)

- Primary Microcephaly 2 With or Without Cortical Malformations

  ### Primary Microcephaly 2 With or Without Cortical Malformations

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 05, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 19:36103467

- Primary autosomal recessive microcephaly 2, Autosomal recessive

  ### Primary autosomal recessive microcephaly 2

  Microcephaly-2 with or without cortical malformations is an autosomal recessive neurodevelopmental disorder showing phenotypic variability. Classically, primary microcephaly is a clinical diagnosis made when an individual has a head circumference more than 3 standard deviations (SD) below the age- and sex-matched population mean, and mental retardation with no other associated malformations and with no apparent etiology (Hofman, 1984). Patients with WDR62 mutations have head circumferences ranging from low-normal to severe (-9.8 SD), and most patients with brain scans have shown various types of cortical malformations. All have delayed psychomotor development; seizures are variable (summary by Yu et al., 2010). For a general phenotypic description and a discussion of genetic heterogeneity of primary microcephaly, see MCPH1 (251200).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 05, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 19:36103467

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 05, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 19:36103467

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (2)

Hetero

CT

Gene: WDR62
Variant: c.3514+44G>A
rsID: rs45468494
Ref Allele: G
Alt Allele: A
Freq: 3.3536%uncommon
CADD: 1.306

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 19:36103251

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: PC
Variant: c.2224-9T>G
rsID: rs45560936
Ref Allele: A
Alt Allele: C
Freq: 3.3743%uncommon
CADD: 5.898

ClinVar Submissions (4)

- Pyruvate carboxylase deficiency, Autosomal recessive

  ### Pyruvate carboxylase deficiency

  Pyruvate carboxylase (PC) deficiency is characterized in most affected individuals by failure to thrive, developmental delay, recurrent seizures, and metabolic acidosis. Three clinical types are recognized: Type A (infantile form), in which most affected children die in infancy or early childhood. Type B (severe neonatal form), in which affected infants have hepatomegaly, pyramidal tract signs, and abnormal movement and die within the first three months of life. Type C (intermittent/benign form), in which affected individuals have normal or mildly delayed neurologic development and episodic metabolic acidosis.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 24, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:66850932

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 24, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:66850932

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 24, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:66850932

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

AC

Gene: AHI1
Variant: c.-214G>A
rsID: rs113052089
Ref Allele: C
Alt Allele: T
Freq: 3.3791%uncommon
CADD: 7.133

ClinVar Submissions (1)

- Joubert syndrome

  ### Joubert syndrome

  Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 6:135497680

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CT

Gene: PIKFYVE
Variant: c.5511T>C
(p.Ile1837=)
rsID: rs13020468
Ref Allele: T
Alt Allele: C
Freq: 3.391%uncommon
CADD: 14.22

ClinVar Submissions (1)

- Fleck corneal dystrophy, Autosomal dominant

  ### Fleck corneal dystrophy

  Fleck corneal dystrophy (CFD) is a rare autosomal dominant disease characterized by numerous tiny, dot-like white flecks scattered in all layers of the corneal stroma. Typically, the stroma located in between the flecks is clear, and the endothelium, the epithelium, Bowman layer, and Descemet membrane are normal. Patients are usually asymptomatic with normal vision, yet a small number of patients report the sensation of a minor photophobia. The flecks in CFD can appear as early as 2 years of age, or sometimes even at birth, and appear not to progress significantly throughout life. Histologically, the corneal flecks appear to correspond to abnormal keratocytes swollen with membrane-limited intracytoplasmic vesicles containing complex lipids and glycosaminoglycans (summary by Kawasaki et al., 2012).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 2:208350847

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

TC

Gene: BDNF
Variant: c.16G>A
(p.Glu6Lys)
rsID: rs66866077
Ref Allele: C
Alt Allele: T
Freq: 3.4236%uncommon
CADD: 10.98

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 21, 2013
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 11:27699390

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (3)

Hetero

CT

Gene: NDUFS5
Variant: c.*18G>A
rsID: rs6981
Ref Allele: G
Alt Allele: A
Freq: 3.4276%uncommon
CADD: 3.097

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 18, 2015
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 1:39034514

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: ATP1A2
Variant: c.*253C>T
rsID: rs78930771
Ref Allele: C
Alt Allele: T
Freq: 3.4452%uncommon
CADD: 5.734

ClinVar Submissions (1)

- Alternating hemiplegia of childhood

  ### Alternating hemiplegia of childhood

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:160141575

- Familial hemiplegic migraine

  ### Familial hemiplegic migraine

  Familial hemiplegic migraine (FHM) falls within the category of migraine with aura. In migraine with aura (including familial hemiplegic migraine) the neurologic symptoms of aura are unequivocally localizable to the cerebral cortex or brain stem and include visual disturbance (most common), sensory loss (e.g., numbness or paresthesias of the face or an extremity), and dysphasia (difficulty with speech); FHM must include motor involvement, i.e., hemiparesis (weakness of an extremity). Hemiparesis occurs with at least one other symptom during FHM aura. Neurologic deficits with FHM attacks can be prolonged for hours to days and may outlast the associated migrainous headache. FHM is often earlier in onset than typical migraine, frequently beginning in the first or second decade; the frequency of attacks tends to decrease with age. Approximately 40%-50% of families with FHM1 have cerebellar signs ranging from nystagmus to progressive, usually late-onset mild ataxia. Cerebral infarction and death have rarely been associated with hemiplegic migraine.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:160141575

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: ATP1A2
Variant: c.1704C>T
(p.Phe568=)
rsID: rs17846714
Ref Allele: C
Alt Allele: T
Freq: 3.4459%uncommon
CADD: 12.49

ClinVar Submissions (6)

- Alternating hemiplegia of childhood

  ### Alternating hemiplegia of childhood

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 14, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:160130474

- Familial hemiplegic migraine

  ### Familial hemiplegic migraine

  Familial hemiplegic migraine (FHM) falls within the category of migraine with aura. In migraine with aura (including familial hemiplegic migraine) the neurologic symptoms of aura are unequivocally localizable to the cerebral cortex or brain stem and include visual disturbance (most common), sensory loss (e.g., numbness or paresthesias of the face or an extremity), and dysphasia (difficulty with speech); FHM must include motor involvement, i.e., hemiparesis (weakness of an extremity). Hemiparesis occurs with at least one other symptom during FHM aura. Neurologic deficits with FHM attacks can be prolonged for hours to days and may outlast the associated migrainous headache. FHM is often earlier in onset than typical migraine, frequently beginning in the first or second decade; the frequency of attacks tends to decrease with age. Approximately 40%-50% of families with FHM1 have cerebellar signs ranging from nystagmus to progressive, usually late-onset mild ataxia. Cerebral infarction and death have rarely been associated with hemiplegic migraine.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 14, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:160130474

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 14, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:160130474

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: ATP1A2
Variant: c.*546G>A
rsID: rs62621782
Ref Allele: G
Alt Allele: A
Freq: 3.4491%uncommon
CADD: 0.141

ClinVar Submissions (1)

- Alternating hemiplegia of childhood

  ### Alternating hemiplegia of childhood

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:160141868

- Familial hemiplegic migraine

  ### Familial hemiplegic migraine

  Familial hemiplegic migraine (FHM) falls within the category of migraine with aura. In migraine with aura (including familial hemiplegic migraine) the neurologic symptoms of aura are unequivocally localizable to the cerebral cortex or brain stem and include visual disturbance (most common), sensory loss (e.g., numbness or paresthesias of the face or an extremity), and dysphasia (difficulty with speech); FHM must include motor involvement, i.e., hemiparesis (weakness of an extremity). Hemiparesis occurs with at least one other symptom during FHM aura. Neurologic deficits with FHM attacks can be prolonged for hours to days and may outlast the associated migrainous headache. FHM is often earlier in onset than typical migraine, frequently beginning in the first or second decade; the frequency of attacks tends to decrease with age. Approximately 40%-50% of families with FHM1 have cerebellar signs ranging from nystagmus to progressive, usually late-onset mild ataxia. Cerebral infarction and death have rarely been associated with hemiplegic migraine.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:160141868

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: PNP
Variant: c.*728T>C
rsID: rs1760933
Ref Allele: T
Alt Allele: C
Freq: 3.4499%uncommon
CADD: 1.51

ClinVar Submissions (1)

- Purine-nucleoside phosphorylase deficiency, Autosomal recessive

  ### Purine-nucleoside phosphorylase deficiency

  Purine nucleoside phosphorylase deficiency is a rare autosomal recessive immunodeficiency disorder characterized mainly by decreased T-cell function. Some patients also have neurologic impairment (review by Aust et al., 1992).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 14:20477329

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

TC

Gene: ARSB
Variant: c.*60G>A
rsID: rs2173012
Ref Allele: C
Alt Allele: T
Freq: 3.4682%uncommon
CADD: 0.842

ClinVar Submissions (1)

- Mucopolysaccharidosis type VI, Autosomal recessive

  ### Mucopolysaccharidosis type VI

  Mucopolysaccharidosis type VI is an autosomal recessive lysosomal storage disorder resulting from a deficiency of arylsulfatase B. Clinical features and severity are variable, but usually include short stature, hepatosplenomegaly, dysostosis multiplex, stiff joints, corneal clouding, cardiac abnormalities, and facial dysmorphism. Intelligence is usually normal (Azevedo et al., 2004).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:78780337

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CT

Gene: CCDC65
Variant: c.505C>A
(p.His169Asn)
rsID: rs79716342
Ref Allele: C
Alt Allele: A
Freq: 3.477%uncommon
CADD: 14.43

ClinVar Submissions (2)

- Ciliary dyskinesia, primary, 27, Autosomal recessive

  ### Ciliary dyskinesia, primary, 27

  Primary ciliary dyskinesia (PCD) is associated with situs abnormalities, abnormal sperm motility, and abnormal ciliary structure and function that result in retention of mucus and bacteria in the respiratory tract leading to chronic otosinopulmonary disease. More than 75% of full-term neonates with PCD have "neonatal respiratory distress" requiring supplemental oxygen for days to weeks. Chronic airway infection, apparent in early childhood, results in bronchiectasis that is almost uniformly present in adulthood. Nasal congestion and sinus infections, apparent in early childhood, persist through adulthood. Chronic/recurrent ear infection, apparent in most young children, can be associated with transient or later irreversible hearing loss. Situs inversus totalis (mirror-image reversal of all visceral organs with no apparent physiologic consequences) is present in 40%-50% of individuals with PCD; heterotaxy (discordance of right and left patterns of ordinarily asymmetric structures that can be associated with significant malformations) is present in approximately 12%. Virtually all males with PCD are infertile as a result of abnormal sperm motility.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 14, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 12:48917004

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 14, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 12:48917004

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

CA

Gene: CCDC65
Variant: c.880C>T
(p.Arg294Cys)
rsID: rs78877829
Ref Allele: C
Alt Allele: T
Freq: 3.4897%uncommon
CADD: 25.2

ClinVar Submissions (2)

- Ciliary dyskinesia, primary, 27, Autosomal recessive

  ### Ciliary dyskinesia, primary, 27

  Primary ciliary dyskinesia (PCD) is associated with situs abnormalities, abnormal sperm motility, and abnormal ciliary structure and function that result in retention of mucus and bacteria in the respiratory tract leading to chronic otosinopulmonary disease. More than 75% of full-term neonates with PCD have "neonatal respiratory distress" requiring supplemental oxygen for days to weeks. Chronic airway infection, apparent in early childhood, results in bronchiectasis that is almost uniformly present in adulthood. Nasal congestion and sinus infections, apparent in early childhood, persist through adulthood. Chronic/recurrent ear infection, apparent in most young children, can be associated with transient or later irreversible hearing loss. Situs inversus totalis (mirror-image reversal of all visceral organs with no apparent physiologic consequences) is present in 40%-50% of individuals with PCD; heterotaxy (discordance of right and left patterns of ordinarily asymmetric structures that can be associated with significant malformations) is present in approximately 12%. Virtually all males with PCD are infertile as a result of abnormal sperm motility.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 14, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 12:48918757

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 14, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 12:48918757

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: MYH9
Variant: c.4563C>T
(p.His1521=)
rsID: rs11549907
Ref Allele: G
Alt Allele: A
Freq: 3.5025%uncommon
CADD: 7.955

ClinVar Submissions (4)

- MYH9-related disorder

  ### MYH9-related disorder

  An autosomal dominant disorder characterized by the triad of thrombocytopenia, giant platelets, and characteristic inclusions in peripheral blood leukocytes, without other organ dysfunction; it is associated with mutation of the MYH9 gene.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 09, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 22:36288934

- Nonsyndromic Hearing Loss, Dominant

  ### Nonsyndromic Hearing Loss, Dominant

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 09, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 22:36288934

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 09, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 22:36288934

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (5)

Hetero

GA

Gene: GRM6
Variant: c.2437-6G>A
rsID: rs114970739
Ref Allele: C
Alt Allele: T
Freq: 3.524%uncommon
CADD: 8.47

ClinVar Submissions (1)

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: no assertion provided
  Number of Submitters: 1
  Clinical Significance: not provided
  Assembly: GRCh38
  Chromosome/Position: 5:178981860

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CT

Gene: GRM6
Variant: c.2436+46A>C
rsID: rs17078872
Ref Allele: T
Alt Allele: G
Freq: 3.528%uncommon
CADD: 2.092

ClinVar Submissions (1)

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: no assertion provided
  Number of Submitters: 1
  Clinical Significance: not provided
  Assembly: GRCh38
  Chromosome/Position: 5:178982864

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

TG

Gene: GRM6
Variant: c.2134A>G
(p.Met712Val)
rsID: rs17078877
Ref Allele: T
Alt Allele: C
Freq: 3.5288%uncommon
CADD: 22.5

ClinVar Submissions (1)

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: no assertion provided
  Number of Submitters: 1
  Clinical Significance: not provided
  Assembly: GRCh38
  Chromosome/Position: 5:178983212

- LitVar
- SNPedia
- dbSNP
- UniProt
- OpenSNP
- PubMed

Hetero

TC

Gene: TRPV4
Variant: c.55C>T
(p.Pro19Ser)
rsID: rs3742030
Ref Allele: G
Alt Allele: A
Freq: 3.5383%uncommon
CADD: 17.14

ClinVar Submissions (8)

- Brachyolmia

  ### Brachyolmia

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 28, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 8
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 12:109814742
  OMIM Allelic Variant: 605427.0012

- Charcot-Marie-Tooth disease type 2C, Autosomal dominant

  ### Charcot-Marie-Tooth disease type 2C

  The TRPV4-associated disorders (previously considered to be clinically distinct phenotypes before their molecular basis was discovered) are now grouped into neuromuscular disorders and skeletal dysplasias; however, the overlap within and between both groups is considerable. Bilateral progressive sensorineural hearing loss (SNHL) can occur in both. The three neuromuscular disorders (mildest to most severe): Charcot-Marie-Tooth disease type 2C (CMT2C). Scapuloperoneal spinal muscular atrophy (SPSMA). Congenital distal spinal muscular atrophy (CDSMA). The neuromuscular disorders are characterized by a progressive peripheral neuropathy with variable combinations of laryngeal dysfunction (i.e., vocal fold paresis), respiratory dysfunction, and joint contractures. The six skeletal dysplasias: Mildest: Familial digital arthropathy-brachydactyly. Intermediate: Autosomal dominant brachyolmia. Spondylometaphyseal dysplasia, Kozlowski type. Spondyloepiphyseal dysplasia, Maroteaux type. Most severe: Parastremmatic dysplasia. Metatropic dysplasia. The skeletal dysplasia is characterized by brachydactyly (in all 6); the five that are more severe have short stature that varies from mild to severe with progressive spinal deformity and involvement of the long bones and pelvis. In the mildest of the TRPV4-associated disorders life span is normal; in the most severe it is shortened.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 28, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 8
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 12:109814742
  OMIM Allelic Variant: 605427.0012

- Charcot-Marie-Tooth disease, type 2

  ### Charcot-Marie-Tooth disease, type 2

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 28, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 8
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 12:109814742
  OMIM Allelic Variant: 605427.0012

- Distal spinal muscular atrophy, congenital nonprogressive, Autosomal dominant

  ### Distal spinal muscular atrophy, congenital nonprogressive

  The TRPV4-associated disorders (previously considered to be clinically distinct phenotypes before their molecular basis was discovered) are now grouped into neuromuscular disorders and skeletal dysplasias; however, the overlap within and between both groups is considerable. Bilateral progressive sensorineural hearing loss (SNHL) can occur in both. The three neuromuscular disorders (mildest to most severe): Charcot-Marie-Tooth disease type 2C (CMT2C). Scapuloperoneal spinal muscular atrophy (SPSMA). Congenital distal spinal muscular atrophy (CDSMA). The neuromuscular disorders are characterized by a progressive peripheral neuropathy with variable combinations of laryngeal dysfunction (i.e., vocal fold paresis), respiratory dysfunction, and joint contractures. The six skeletal dysplasias: Mildest: Familial digital arthropathy-brachydactyly. Intermediate: Autosomal dominant brachyolmia. Spondylometaphyseal dysplasia, Kozlowski type. Spondyloepiphyseal dysplasia, Maroteaux type. Most severe: Parastremmatic dysplasia. Metatropic dysplasia. The skeletal dysplasia is characterized by brachydactyly (in all 6); the five that are more severe have short stature that varies from mild to severe with progressive spinal deformity and involvement of the long bones and pelvis. In the mildest of the TRPV4-associated disorders life span is normal; in the most severe it is shortened.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 28, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 8
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 12:109814742
  OMIM Allelic Variant: 605427.0012

- Metatrophic dysplasia, Autosomal dominant

  ### Metatrophic dysplasia

  The TRPV4-associated disorders (previously considered to be clinically distinct phenotypes before their molecular basis was discovered) are now grouped into neuromuscular disorders and skeletal dysplasias; however, the overlap within and between both groups is considerable. Bilateral progressive sensorineural hearing loss (SNHL) can occur in both. The three neuromuscular disorders (mildest to most severe): Charcot-Marie-Tooth disease type 2C (CMT2C). Scapuloperoneal spinal muscular atrophy (SPSMA). Congenital distal spinal muscular atrophy (CDSMA). The neuromuscular disorders are characterized by a progressive peripheral neuropathy with variable combinations of laryngeal dysfunction (i.e., vocal fold paresis), respiratory dysfunction, and joint contractures. The six skeletal dysplasias: Mildest: Familial digital arthropathy-brachydactyly. Intermediate: Autosomal dominant brachyolmia. Spondylometaphyseal dysplasia, Kozlowski type. Spondyloepiphyseal dysplasia, Maroteaux type. Most severe: Parastremmatic dysplasia. Metatropic dysplasia. The skeletal dysplasia is characterized by brachydactyly (in all 6); the five that are more severe have short stature that varies from mild to severe with progressive spinal deformity and involvement of the long bones and pelvis. In the mildest of the TRPV4-associated disorders life span is normal; in the most severe it is shortened.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 28, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 8
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 12:109814742
  OMIM Allelic Variant: 605427.0012

- Scapuloperoneal spinal muscular atrophy, Autosomal dominant

  ### Scapuloperoneal spinal muscular atrophy

  The TRPV4-associated disorders (previously considered to be clinically distinct phenotypes before their molecular basis was discovered) are now grouped into neuromuscular disorders and skeletal dysplasias; however, the overlap within and between both groups is considerable. Bilateral progressive sensorineural hearing loss (SNHL) can occur in both. The three neuromuscular disorders (mildest to most severe): Charcot-Marie-Tooth disease type 2C (CMT2C). Scapuloperoneal spinal muscular atrophy (SPSMA). Congenital distal spinal muscular atrophy (CDSMA). The neuromuscular disorders are characterized by a progressive peripheral neuropathy with variable combinations of laryngeal dysfunction (i.e., vocal fold paresis), respiratory dysfunction, and joint contractures. The six skeletal dysplasias: Mildest: Familial digital arthropathy-brachydactyly. Intermediate: Autosomal dominant brachyolmia. Spondylometaphyseal dysplasia, Kozlowski type. Spondyloepiphyseal dysplasia, Maroteaux type. Most severe: Parastremmatic dysplasia. Metatropic dysplasia. The skeletal dysplasia is characterized by brachydactyly (in all 6); the five that are more severe have short stature that varies from mild to severe with progressive spinal deformity and involvement of the long bones and pelvis. In the mildest of the TRPV4-associated disorders life span is normal; in the most severe it is shortened.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 28, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 8
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 12:109814742
  OMIM Allelic Variant: 605427.0012

- Sodium serum level quantitative trait locus 1

  ### Sodium serum level quantitative trait locus 1

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 28, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 8
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 12:109814742
  OMIM Allelic Variant: 605427.0012

- Spondylometaphyseal dysplasia, Autosomal dominant

  ### Spondylometaphyseal dysplasia

  The Strudwick type of spondyloepimetaphyseal dysplasia (SEMD) is characterized by disproportionate short stature, pectus carinatum, and scoliosis, as well as dappled metaphyses (summary by Tiller et al., 1995).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 28, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 8
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 12:109814742
  OMIM Allelic Variant: 605427.0012

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 28, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 8
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 12:109814742
  OMIM Allelic Variant: 605427.0012

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 28, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 8
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 12:109814742
  OMIM Allelic Variant: 605427.0012

Benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (3)

Hetero

GA

Gene: FBN2
Variant: c.*819A>G
rsID: rs72783099
Ref Allele: T
Alt Allele: C
Freq: 3.5407%uncommon
CADD: 5.971

ClinVar Submissions (1)

- Congenital contractural arachnodactyly, Autosomal dominant

  ### Congenital contractural arachnodactyly

  Congenital contractural arachnodactyly (CCA) is characterized by a Marfan-like appearance (tall, slender habitus in which arm span exceeds height) and long, slender fingers and toes (arachnodactyly). Most affected individuals have "crumpled" ears that present as a folded upper helix of the external ear and most have contractures of major joints (knees and ankles) at birth. The proximal interphalangeal joints also have flexion contractures (i.e., camptodactyly), as do the toes. Hip contractures, adducted thumbs, and clubfoot may occur. The majority of affected individuals have muscular hypoplasia. Contractures usually improve with time. Kyphosis/scoliosis is present in about half of all affected individuals. It begins as early as infancy, is progressive, and causes the greatest morbidity in CCA. Dilatation of the aorta is occasionally present. Infants have been observed with a severe/lethal form characterized by multiple cardiovascular and gastrointestinal anomalies in addition to the typical skeletal findings.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:128258636

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

TC

Gene: PIK3R2
Variant: c.903G>A
(p.Ala301=)
rsID: rs28730848
Ref Allele: G
Alt Allele: A
Freq: 3.5558%uncommon
CADD: 6.198

ClinVar Submissions (2)

- Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, Autosomal dominant

  ### Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1

  The MPPH syndrome is a developmental brain disorder characterized by megalencephaly (brain overgrowth) with the cortical malformation bilateral perisylvian polymicrogyria (BPP). At birth the occipital frontal circumference (OFC) ranges from normal to 6 standard deviations (SD) above the mean for age, sex, and gestational age; in older individuals the range is from 3 to 10 SD above the mean. A variable degree of ventriculomegaly is seen in almost all children with MPPH syndrome; nearly 50% of those have frank hydrocephalus. Neurologic problems associated with BPP include oromotor dysfunction (100%), epilepsy (50%), and mild to severe intellectual disability (100%). Postaxial hexadactyly occurs in 50% of individuals with MPPH syndrome.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 28, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 19:18162203

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GA

Gene: LAMB2
Variant: c.2740G>A
(p.Gly914Arg)
rsID: rs35713889
Ref Allele: C
Alt Allele: T
Freq: 3.5614%uncommon
CADD: 27.9

ClinVar Submissions (5)

- Nephrotic syndrome

  ### Nephrotic syndrome

  A collection of symptoms that include severe edema, proteinuria, and hypoalbuminemia; it is indicative of renal dysfunction.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 02, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 3:49125150

- Nephrotic syndrome, type 5, with or without ocular abnormalities, Autosomal recessive

  ### Nephrotic syndrome, type 5, with or without ocular abnormalities

  Nephrotic syndrome type 5 is an autosomal recessive disorder characterized by very early onset of progressive renal failure manifest as proteinuria with consecutive edema starting in utero or within the first 3 months of life. A subset of patients may develop mild ocular anomalies, such as myopia, nystagmus, and strabismus (summary by Hasselbacher et al., 2006). Mutation in the LAMB2 gene can also cause Pierson syndrome (609049), which is characterized by nephrotic syndrome, distinct ocular anomalies, namely microcoria, and neurodevelopmental delay. For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome, see NPHS1 (256300).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 02, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 3:49125150

- Pierson syndrome, Autosomal recessive

  ### Pierson syndrome

  Pierson syndrome is an autosomal recessive disorder comprising congenital nephrotic syndrome with diffuse mesangial sclerosis and distinct ocular abnormalities, including microcoria and hypoplasia of the ciliary and pupillary muscles, as well as other anomalies. Many patients die early, and those who survive tend to show neurodevelopmental delay and visual loss (summary by Zenker et al., 2004). Mutations in the LAMB2 gene also cause nephrotic syndrome type 5 with or without mild ocular anomalies (NPHS5; 614199).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 02, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 3:49125150

- Pierson syndrome, Autosomal recessive

  ### Pierson syndrome

  Pierson syndrome is an autosomal recessive disorder comprising congenital nephrotic syndrome with diffuse mesangial sclerosis and distinct ocular abnormalities, including microcoria and hypoplasia of the ciliary and pupillary muscles, as well as other anomalies. Many patients die early, and those who survive tend to show neurodevelopmental delay and visual loss (summary by Zenker et al., 2004). Mutations in the LAMB2 gene also cause nephrotic syndrome type 5 with or without mild ocular anomalies (NPHS5; 614199).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 02, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 3:49125150

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 02, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 3:49125150

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 02, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 3:49125150

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (2)

Hetero

CT

Gene: SCO2;TYMP
Variant: c.1393G>A
(p.Ala465Thr)
rsID: rs112723255
Ref Allele: C
Alt Allele: T
Freq: 3.5797%uncommon
CADD: 15.49

ClinVar Submissions (6)

- Fatal Infantile Cardioencephalomyopathy

  ### Fatal Infantile Cardioencephalomyopathy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 02, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 22:50525826

- Mitochondrial DNA depletion syndrome 1 (MNGIE type), Autosomal recessive

  ### Mitochondrial DNA depletion syndrome 1 (MNGIE type)

  Mitochondrial neurogastrointestinal encephalopathy (MNGIE) disease is characterized by progressive gastrointestinal dysmotility (manifesting as early satiety, nausea, dysphagia, gastroesophageal reflux, postprandial emesis, episodic abdominal pain and/or distention, and diarrhea); cachexia; ptosis/ophthalmoplegia or ophthalmoparesis; leukoencephalopathy; and demyelinating peripheral neuropathy (manifesting as paresthesias (tingling, numbness, and pain) and symmetric and distal weakness more prominently affecting the lower extremities). The order in which manifestations appear is unpredictable. Onset is usually between the first and fifth decades; in about 60% of individuals, symptoms begin before age 20 years.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 02, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 22:50525826

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 02, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 22:50525826

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 02, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 22:50525826

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CT

Gene: WDR62
Variant: c.562-13C>T
rsID: rs78138007
Ref Allele: C
Alt Allele: T
Freq: 3.5845%uncommon
CADD: 6.8

ClinVar Submissions (3)

- Primary Microcephaly 2 With or Without Cortical Malformations

  ### Primary Microcephaly 2 With or Without Cortical Malformations

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 19:36067293

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 19:36067293

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (2)

Hetero

CT

Gene: WDR62
Variant: c.3401T>G
(p.Met1134Arg)
rsID: rs61741470
Ref Allele: T
Alt Allele: G
Freq: 3.5845%uncommon
CADD: 1.547

ClinVar Submissions (4)

- Primary Microcephaly 2 With or Without Cortical Malformations

  ### Primary Microcephaly 2 With or Without Cortical Malformations

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 05, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 19:36103013

- Primary autosomal recessive microcephaly 2, Autosomal recessive

  ### Primary autosomal recessive microcephaly 2

  Microcephaly-2 with or without cortical malformations is an autosomal recessive neurodevelopmental disorder showing phenotypic variability. Classically, primary microcephaly is a clinical diagnosis made when an individual has a head circumference more than 3 standard deviations (SD) below the age- and sex-matched population mean, and mental retardation with no other associated malformations and with no apparent etiology (Hofman, 1984). Patients with WDR62 mutations have head circumferences ranging from low-normal to severe (-9.8 SD), and most patients with brain scans have shown various types of cortical malformations. All have delayed psychomotor development; seizures are variable (summary by Yu et al., 2010). For a general phenotypic description and a discussion of genetic heterogeneity of primary microcephaly, see MCPH1 (251200).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 05, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 19:36103013

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 05, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 19:36103013

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (2)

Hetero

TG

Gene: WDR62
Variant: c.1233+13C>T
rsID: rs76130844
Ref Allele: C
Alt Allele: T
Freq: 3.5877%uncommon
CADD: 0.021

ClinVar Submissions (3)

- Primary Microcephaly 2 With or Without Cortical Malformations

  ### Primary Microcephaly 2 With or Without Cortical Malformations

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 19:36073544

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 19:36073544

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (2)

Hetero

CT

Gene: SYNE4
Variant: c.819T>C
(p.Cys273=)
rsID: rs2285423
Ref Allele: A
Alt Allele: G
Freq: 3.6092%uncommon
CADD: 14.86

ClinVar Submissions (2)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 09, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 19:36006471

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

AG

Gene: ADGRV1
Variant: c.12927G>A
(p.Ala4309=)
rsID: rs35092519
Ref Allele: G
Alt Allele: A
Freq: 3.618%uncommon
CADD: 0.03

ClinVar Submissions (4)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 23, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 5:90778942

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: NALCN
Variant: c.1836A>G
(p.Lys612=)
rsID: rs17582557
Ref Allele: T
Alt Allele: C
Freq: 3.6315%uncommon
CADD: 12.1

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 13:101176303

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

TC

Gene: GHSR
Variant: c.447C>G
(p.Leu149=)
rsID: rs2232169
Ref Allele: G
Alt Allele: C
Freq: 3.6538%uncommon
CADD: 7.244

ClinVar Submissions (1)

- Short stature, idiopathic, autosomal, Autosomal dominant

  ### Short stature, idiopathic, autosomal

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 3:172447967

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (4)

Hetero

GC

Gene: PLN
Variant: c.-211-19A>C
rsID: rs77186188
Ref Allele: A
Alt Allele: C
Freq: 3.6554%uncommon
CADD: 12.52

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 28, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 6:118548260

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

AC

Gene: PIEZO1
Variant: c.1013C>A
(p.Ser338Tyr)
rsID: rs112081600
Ref Allele: G
Alt Allele: T
Freq: 3.6657%uncommon
CADD: 12.38

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 13, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 16:88737941

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GT

Gene: STRC
Variant: c.4562G>A
(p.Arg1521Gln)
rsID: rs74643365
Ref Allele: C
Alt Allele: T
Freq: 3.6713%uncommon
CADD: 15.06

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 07, 2012
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 15:43601535

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: SERPINF2
Variant: c.186C>T
(p.Ala62=)
rsID: rs35259159
Ref Allele: C
Alt Allele: T
Freq: 3.7064%uncommon
CADD: 2.333

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 17:1745728

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: MTTP
Variant: c.1769+14C>T
rsID: rs41275713
Ref Allele: C
Alt Allele: T
Freq: 3.7231%uncommon
CADD: 1.013

ClinVar Submissions (2)

- Abetalipoproteinaemia, Autosomal recessive

  ### Abetalipoproteinaemia

  Abetalipoproteinemia typically presents in infancy with failure to thrive, diarrhea, vomiting, and malabsorption of fat. Hematologic manifestations may include acanthocytosis (irregularly spiculated erythrocytes), anemia, reticulocytosis, and hemolysis with resultant hyperbilirubinemia. Malabsorption of fat-soluble vitamins (A, D, E, and K) can result in an increased international normalized ratio (INR). Untreated individuals may develop atypical pigmentation of the retina that may present with progressive loss of night vision and/or color vision in adulthood. Neuromuscular findings in untreated individuals including progressive loss of deep tendon reflexes, vibratory sense, and proprioception; muscle weakness; dysarthria; and ataxia typically manifest in the first or second decades of life.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 4:99608991

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CT

Gene: MTTP
Variant: c.730C>G
(p.Gln244Glu)
rsID: rs17599091
Ref Allele: C
Alt Allele: G
Freq: 3.7239%uncommon
CADD: 5.607

ClinVar Submissions (3)

- Abetalipoproteinaemia, Autosomal recessive

  ### Abetalipoproteinaemia

  Abetalipoproteinemia typically presents in infancy with failure to thrive, diarrhea, vomiting, and malabsorption of fat. Hematologic manifestations may include acanthocytosis (irregularly spiculated erythrocytes), anemia, reticulocytosis, and hemolysis with resultant hyperbilirubinemia. Malabsorption of fat-soluble vitamins (A, D, E, and K) can result in an increased international normalized ratio (INR). Untreated individuals may develop atypical pigmentation of the retina that may present with progressive loss of night vision and/or color vision in adulthood. Neuromuscular findings in untreated individuals including progressive loss of deep tendon reflexes, vibratory sense, and proprioception; muscle weakness; dysarthria; and ataxia typically manifest in the first or second decades of life.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 4:99591762

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 4:99591762

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed

Hetero

CG

Gene: ABRAXAS1
Variant: c.1117G>A
(p.Asp373Asn)
rsID: rs13125836
Ref Allele: C
Alt Allele: T
Freq: 3.7279%uncommon
CADD: 20.8

ClinVar Submissions (2)

- Hereditary cancer-predisposing syndrome

  ### Hereditary cancer-predisposing syndrome

  The condition of a pattern of malignancies within a family, but not every individual's necessarily having the same neoplasm. Characteristically the tumor tends to occur at an earlier than average age, individuals may have more than one primary tumor, the tumors may be multicentric, usually more than 25 percent of the individuals in direct lineal descent from the proband are affected, and the cancer predisposition in these families behaves as an autosomal dominant trait with about 60 percent penetrance.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 01, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 4:83462582

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 01, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 4:83462582

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (3)

Hetero

CT

Gene: FGFR3
Variant: c.1075+30G>C
rsID: rs3135886
Ref Allele: G
Alt Allele: C
Freq: 3.7764%uncommon
CADD: 0.726

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 4:1803866

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

GC

Gene: KMT2A
Variant: c.5679A>G
(p.Leu1893=)
rsID: rs7107305
Ref Allele: A
Alt Allele: G
Freq: 3.8346%uncommon
CADD: 17.18

ClinVar Submissions (2)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 19, 2013
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 11:118497950

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (2)

Hetero

AG

Gene: KMT2A
Variant: c.4284A>C
(p.Ile1428=)
rsID: rs9332801
Ref Allele: A
Alt Allele: C
Freq: 3.8529%uncommon
CADD: 19.38

ClinVar Submissions (2)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Nov 19, 2013
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 11:118484927

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (2)

Hetero

AC

Gene: TNFRSF11A
Variant: c.933A>G
(p.Thr311=)
rsID: rs8092336
Ref Allele: A
Alt Allele: G
Freq: 3.8529%uncommon
CADD: 0.995

ClinVar Submissions (3)

- Osteopetrosis

  ### Osteopetrosis

  A rare genetic disorder inherited in an autosomal dominant, autosomal recessive, or X-linked recessive pattern. In the majority of cases it is caused by mutations in the CLCN7, TCIRG1, or IKBKG genes. It is characterized by excessive bone formation due to the failure of osteoclasts to resorb bone. It manifests with deformities, fractures, hepatosplenomegaly, anemia, and extramedullary hematopoiesis.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 18:62368850

- Paget disease of bone

  ### Paget disease of bone

  Paget disease of bone is a disorder that causes bones to grow larger and weaker than normal. Affected bones may be misshapen and easily broken (fractured).The classic form of Paget disease of bone typically appears in middle age or later. It usually occurs in one or a few bones and does not spread from one bone to another. Any bones can be affected, although the disease most commonly affects bones in the spine, pelvis, skull, or legs.Many people with classic Paget disease of bone do not experience any symptoms associated with their bone abnormalities. The disease is often diagnosed unexpectedly by x-rays or laboratory tests done for other reasons. People who develop symptoms are most likely to experience pain. The affected bones may themselves be painful, or pain may be caused by arthritis in nearby joints. Arthritis results when the distortion of bones, particularly weight-bearing bones in the legs, causes extra wear and tear on the joints. Arthritis most frequently affects the knees and hips in people with this disease.Other complications of Paget disease of bone depend on which bones are affected. If the disease occurs in bones of the skull, it can cause an enlarged head, hearing loss, headaches, and dizziness. If the disease affects bones in the spine, it can lead to numbness and tingling (due to pinched nerves) and abnormal spinal curvature. In the leg bones, the disease can cause bowed legs and difficulty walking.A rare type of bone cancer called osteosarcoma has been associated with Paget disease of bone. This type of cancer probably occurs in less than 1 in 1,000 people with this disease.Early-onset Paget disease of bone is a less common form of the disease that appears in a person's teens or twenties. Its features are similar to those of the classic form of the disease, although it is more likely to affect the skull, spine, and ribs (the axial skeleton) and the small bones of the hands. The early-onset form of the disorder is also associated with hearing loss early in life.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 18:62368850

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 18:62368850

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (5)

Hetero

AG

Gene: MSH2
Variant: c.1387-250G>A
rsID: rs6741393
Ref Allele: G
Alt Allele: A
Freq: 3.8648%uncommon
CADD: 0.088

ClinVar Submissions (1)

- Lynch syndrome

  ### Lynch syndrome

  Lynch syndrome is characterized by an increased risk for colorectal cancer (CRC) and cancers of the endometrium, stomach, ovary, small bowel, hepatobiliary tract, urinary tract, brain, and skin. In individuals with Lynch syndrome the following lifetime risks for cancer are seen: CRC: 52%-82% (mean age at diagnosis 44-61 years). Endometrial cancer in females: 25%-60% (mean age at diagnosis 48-62 years). Gastric cancer: 6%-13% (mean age at diagnosis 56 years). Ovarian cancer: 4%-12% (mean age at diagnosis 42.5 years; ~30% are diagnosed < age 40 years). The risk for other Lynch syndrome-related cancers is lower, though substantially increased over general population rates.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 05, 2013
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 2:47462781

Expert Reviewed Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (2)

Hetero

GA

Gene: IGLL1
Variant: c.485T>A
(p.Met162Lys)
rsID: rs111903752
Ref Allele: A
Alt Allele: T
Freq: 3.8696%uncommon
CADD: 14.53

ClinVar Submissions (2)

- Agammaglobulinemia 2, autosomal recessive, Autosomal recessive

  ### Agammaglobulinemia 2, autosomal recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 31, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 22:23573423

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 31, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 22:23573423

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

AT

Gene: PKHD1
Variant: c.1185T>C
(p.Asp395=)
rsID: rs1896976
Ref Allele: A
Alt Allele: G
Freq: 3.8855%uncommon
CADD: 8.908

ClinVar Submissions (5)

- Autosomal recessive polycystic kidney disease, Autosomal recessive

  ### Autosomal recessive polycystic kidney disease

  Autosomal recessive polycystic kidney disease (ARPKD) belongs to a group of congenital hepatorenal fibrocystic syndromes and is a cause of significant renal and liver-related morbidity and mortality in children. The majority of individuals with ARPKD present in the neonatal period with enlarged echogenic kidneys. Renal disease is characterized by nephromegaly, hypertension, and varying degrees of renal dysfunction. More than 50% of affected individuals with ARPKD progress to end-stage renal disease (ESRD) within the first decade of life; ESRD may require kidney transplantation. Pulmonary hypoplasia resulting from oligohydramnios occurs in a number of affected infants. Approximately 30% of these infants die in the neonatal period or within the first year of life from respiratory insufficiency or superimposed pulmonary infections. With neonatal respiratory support and renal replacement therapies, the long-term survival of these infants has improved to greater than 80%. As advances in renal replacement therapy and kidney transplantation improve long-term survival, it is likely that clinical hepatobiliary disease will become a major feature of the natural history of ARPKD. In addition, a subset of individuals with this disorder are identified with hepatosplenomegaly; the renal disease is often mild and may be discovered incidentally during imaging studies of the abdomen. Approximately 50% of infants will have clinical evidence of liver involvement at diagnosis although histologic hepatic fibrosis is invariably present at birth. This can lead to progressive portal hypertension with resulting esophageal or gastric varices, enlarged hemorrhoids, splenomegaly, hypersplenism, protein-losing enteropathy, and gastrointestinal bleeding. Other hepatic findings include nonobstructed dilatation of the intrahepatic bile ducts (Caroli syndrome) and dilatation of the common bile duct, which may lead to recurrent or persistent bacterial ascending cholangitis due to dilated bile ducts and stagnant bile flow. An increasing number of affected individuals surviving the neonatal period will eventually require portosystemic shunting or liver transplantation for complications of portal hypertension or cholangitis. The classic neonatal presentation of ARPKD notwithstanding, there is significant variability in age and presenting clinical symptoms related to the relative degree of renal and biliary abnormalities.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 6:52059976

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 6:52059976

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (6)

Hetero

AG

Gene: CASD1;SGCE
Variant: c.1295G>A
(p.Ser432Asn)
rsID: rs559235992
Ref Allele: C
Alt Allele: T
Freq: 3.8927%uncommon
CADD: 0.002

ClinVar Submissions (1)

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 21, 2015
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 7:94597963

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: CLCN5
Variant: c.*2860T>C
rsID: rs140913229
Ref Allele: T
Alt Allele: C
Freq: 3.9055%uncommon

ClinVar Submissions (1)

- Dent's disease

  ### Dent's disease

  Dent disease, an X-linked disorder of proximal renal tubular dysfunction, is characterized by low molecular-weight (LMW) proteinuria, hypercalciuria, and at least one additional finding including nephrocalcinosis, nephrolithiasis, hematuria, hypophosphatemia, chronic kidney disease (CKD), and evidence of X-linked inheritance. Males younger than age ten years may manifest only LMW proteinuria and/or hypercalciuria, which are usually asymptomatic. Thirty to 80% of affected males develop end-stage renal disease (ESRD) between ages 30 and 50 years; in some instances ESRD does not develop until the sixth decade of life or later. The disease may also be accompanied by rickets or osteomalacia, growth restriction, and short stature. Disease severity can vary within the same family. Males with Dent disease 2 (caused by pathogenic variants in OCRL) may also have mild intellectual disability, cataracts, and/or elevated muscle enzymes. Due to random X-chromosome inactivation, some female carriers may manifest hypercalciuria and, rarely, renal calculi and moderate LMW proteinuria. Females rarely develop CKD.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: X:50095079

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Homo

CC

Gene: CHMP1A
Variant: c.*100T>G
rsID: rs117555004
Ref Allele: A
Alt Allele: C
Freq: 3.9381%uncommon
CADD: 3.128

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 11, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 16:89645966

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

AC

Gene: CHMP1A
Variant: c.*94C>T
rsID: rs116954456
Ref Allele: G
Alt Allele: A
Freq: 3.9429%uncommon
CADD: 3.183

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 11, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 16:89645972

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: CHMP1A
Variant: c.106-11G>C
rsID: rs3815949
Ref Allele: C
Alt Allele: G
Freq: 3.9461%uncommon
CADD: 0.003

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 11, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 16:89649508

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CG

Gene: INF2
Variant: c.1227G>T
(p.Ser409=)
rsID: rs3809455
Ref Allele: G
Alt Allele: T
Freq: 3.9501%uncommon
CADD: 2.458

ClinVar Submissions (3)

- Focal segmental glomerulosclerosis

  ### Focal segmental glomerulosclerosis

  A clinicopathological syndrome or diagnostic term for a type of glomerular injury that has multiple causes, primary or secondary. Clinical features include PROTEINURIA, reduced GLOMERULAR FILTRATION RATE, and EDEMA. Kidney biopsy initially indicates focal segmental glomerular consolidation (hyalinosis) or scarring which can progress to globally sclerotic glomeruli leading to eventual KIDNEY FAILURE.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 06, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 14:104707494

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Sep 06, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 14:104707494

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GT

Gene: FAM20A
Variant: c.39G>A
(p.Leu13=)
rsID: rs2907388
Ref Allele: C
Alt Allele: T
Freq: 3.9532%uncommon
CADD: 19.2

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 17:68600628

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: GHSR
Variant: c.60C>T
(p.Asp20=)
rsID: rs2232165
Ref Allele: G
Alt Allele: A
Freq: 3.954%uncommon
CADD: 1.255

ClinVar Submissions (1)

- Short stature, idiopathic, autosomal, Autosomal dominant

  ### Short stature, idiopathic, autosomal

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 3:172448354

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (6)

Hetero

GA

Gene: SFTPA2
Variant: c.148G>C
(p.Val50Leu)
rsID: rs192907309
Ref Allele: C
Alt Allele: G
Freq: 3.9676%uncommon
CADD: 0.018

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 12, 2015
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 10:79559336

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

CG

Gene: BFSP2
Variant: c.1220C>A
(p.Ala407Asp)
rsID: rs79087781
Ref Allele: C
Alt Allele: A
Freq: 3.97%uncommon
CADD: 23

ClinVar Submissions (3)

- Cataract

  ### Cataract

  A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule. [HPO:probinson]

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 10, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 3:133472541

- Cataract 12, multiple types, Autosomal dominant

  ### Cataract 12, multiple types

  Mutations in the BFSP2 gene have been found to cause multiple types of cataract, which have been described as juvenile-onset lamellar, cortical, nuclear embryonic; and congenital nuclear, sutural, stellate, Y-sutural, and punctate cortical.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 10, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 3:133472541

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 10, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 3:133472541

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

CA

Gene: ARSH
Variant: c.653C>T
(p.Thr218Ile)
rsID: rs61997197
Ref Allele: C
Alt Allele: T
Freq: 3.9843%uncommon

ClinVar Submissions (1)

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 30, 2017
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: X:3015282

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Homo

TT

Gene: ARSH
Variant: c.641G>A
(p.Ser214Asn)
rsID: rs61995728
Ref Allele: G
Alt Allele: A
Freq: 3.9851%uncommon

ClinVar Submissions (1)

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 30, 2017
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: X:3015270

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Homo

AA

Gene: ARSH
Variant: c.387T>C
(p.Cys129=)
rsID: rs143359225
Ref Allele: T
Alt Allele: C
Freq: 3.9875%uncommon

ClinVar Submissions (1)

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 30, 2017
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: X:3015016

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Homo

CC

Gene: GHSR
Variant: c.*796A>T
rsID: rs58550930
Ref Allele: T
Alt Allele: A
Freq: 3.9923%uncommon
CADD: 0.219

ClinVar Submissions (1)

- Short stature, idiopathic, autosomal, Autosomal dominant

  ### Short stature, idiopathic, autosomal

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 3:172444365

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

TA

Gene: DHCR7
Variant: c.-23T>C
rsID: rs12573951
Ref Allele: A
Alt Allele: G
Freq: 4.0544%uncommon
CADD: 3.983

ClinVar Submissions (1)

- Smith-Lemli-Opitz syndrome, Autosomal recessive

  ### Smith-Lemli-Opitz syndrome

  Smith-Lemli-Opitz syndrome (SLOS) is a congenital multiple anomaly syndrome caused by an abnormality in cholesterol metabolism resulting from deficiency of the enzyme 7-dehydrocholesterol (7-DHC) reductase. It is characterized by prenatal and postnatal growth retardation, microcephaly, moderate to severe intellectual disability, and multiple major and minor malformations. The malformations include distinctive facial features, cleft palate, cardiac defects, underdeveloped external genitalia in males, postaxial polydactyly, and 2-3 syndactyly of the toes. The clinical spectrum is wide and individuals have been described with normal development and only minor malformations.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:71447626

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

AG

Gene: PMM2
Variant: c.*1516C>G
rsID: rs74008088
Ref Allele: C
Alt Allele: G
Freq: 4.0631%uncommon
CADD: 0.76

ClinVar Submissions (1)

- Congenital disorder of glycosylation

  ### Congenital disorder of glycosylation

  A genetically heterogeneous group of heritable disorders resulting from defects in protein N-glycosylation.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 16:8849341

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CG

Gene: ITGB3
Variant: c.*671C>T
rsID: rs16941864
Ref Allele: C
Alt Allele: T
Freq: 4.099%uncommon
CADD: 8.846

ClinVar Submissions (1)

- Glanzmann thrombasthenia, Autosomal recessive

  ### Glanzmann thrombasthenia

  Glanzmann thrombasthenia is an autosomal recessive bleeding disorder characterized by failure of platelet aggregation and by absent or diminished clot retraction. The abnormalities are related to quantitative or qualitative abnormalities of the GPIIb/IIIa platelet surface fibrinogen receptor complex resulting from mutations in either the GPIIb or GPIIIa genes (Rosenberg et al., 1997). See 187800 for discussion of a possible dominant form.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 17:47310875

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CT

Gene: SGCD
Variant: c.290G>A
(p.Arg97Gln)
rsID: rs45559835
Ref Allele: G
Alt Allele: A
Freq: 4.1133%uncommon
CADD: 24.7

ClinVar Submissions (9)

- Cardiovascular phenotype

  ### Cardiovascular phenotype

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 08, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:156508698

- Delta-sarcoglycanopathy

  ### Delta-sarcoglycanopathy

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 08, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:156508698

- Dilated Cardiomyopathy, Dominant

  ### Dilated Cardiomyopathy, Dominant

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 08, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:156508698

- Limb-Girdle Muscular Dystrophy, Recessive

  ### Limb-Girdle Muscular Dystrophy, Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 08, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:156508698

- Limb-girdle muscular dystrophy, type 2F, Autosomal recessive

  ### Limb-girdle muscular dystrophy, type 2F

  Limb-girdle muscular dystrophy is a term for a group of diseases that cause weakness and wasting of the muscles in the arms and legs. The muscles most affected are those closest to the body (proximal muscles), specifically the muscles of the shoulders, upper arms, pelvic area, and thighs.The severity, age of onset, and features of limb-girdle muscle dystrophy vary among the many subtypes of this condition and may be inconsistent even within the same family. Signs and symptoms may first appear at any age and generally worsen with time, although in some cases they remain mild.In the early stages of limb-girdle muscular dystrophy, affected individuals may have an unusual walking gait, such as waddling or walking on the balls of their feet, and may also have difficulty running. They may need to use their arms to press themselves up from a squatting position because of their weak thigh muscles. As the condition progresses, people with limb-girdle muscular dystrophy may eventually require wheelchair assistance.Muscle wasting may cause changes in posture or in the appearance of the shoulder, back, and arm. In particular, weak shoulder muscles tend to make the shoulder blades (scapulae) "stick out" from the back, a sign known as scapular winging. Affected individuals may also have an abnormally curved lower back (lordosis) or a spine that curves to the side (scoliosis). Some develop joint stiffness (contractures) that can restrict movement in their hips, knees, ankles, or elbows. Overgrowth (hypertrophy) of the calf muscles occurs in some people with limb-girdle muscular dystrophy.Weakening of the heart muscle (cardiomyopathy) occurs in some forms of limb-girdle muscular dystrophy. Some affected individuals experience mild to severe breathing problems related to the weakness of muscles needed for breathing. In some cases, the breathing problems are severe enough that affected individuals need to use a machine to help them breathe (mechanical ventilation).Intelligence is generally unaffected in limb-girdle muscular dystrophy; however, developmental delay and intellectual disability have been reported in rare forms of the disorder.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 08, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:156508698

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 08, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:156508698

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (4)

Hetero

GA

Gene: HGSNAT
Variant: c.*1780C>T
rsID: rs1058608
Ref Allele: C
Alt Allele: T
Freq: 4.1292%uncommon
CADD: 5.591

ClinVar Submissions (1)

- Sanfilippo syndrome

  ### Sanfilippo syndrome

  Mucopolysaccharidosis type III (MPS III), also known as Sanfilippo syndrome, is a progressive disorder that primarily affects the brain and spinal cord (central nervous system). Other body systems can also be involved.People with MPS III generally do not display any features of the condition at birth, but they begin to show signs and symptoms of the disorder during early childhood. Affected children often initially have delayed speech and behavior problems. They may become restless, destructive, anxious, or aggressive, and some display features of autism spectrum disorder, which is a condition characterized by difficulty with social interactions and communication. Sleep disturbances are also very common in children with MPS III. This condition causes progressive intellectual disability and the loss of previously acquired skills (developmental regression). In later stages of the disorder, people with MPS III may develop seizures and movement disorders.The physical features of MPS III are less pronounced than those of other types of mucopolysaccharidosis. Individuals with MPS III typically have mildly "coarse" facial features, a large head (macrocephaly), a slightly enlarged liver (mild hepatomegaly), and a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia). Some people with MPS III have short stature, joint stiffness, or mild dysostosis multiplex, which refers to multiple skeletal abnormalities seen on x-ray. Affected individuals often experience chronic diarrhea and recurrent upper respiratory and ear infections. People with MPS III may also have hearing loss and vision problems.MPS III is divided into types IIIA, IIIB, IIIC, and IIID, which are distinguished by their genetic cause. The different types of MPS III have similar signs and symptoms, although the features of MPS IIIA typically appear earlier in life and progress more rapidly. People with MPS III usually live into adolescence or early adulthood.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 8:43201349

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CT

Gene: DRC1
Variant: c.2200G>A
(p.Val734Met)
rsID: rs35313480
Ref Allele: G
Alt Allele: A
Freq: 4.1428%uncommon
CADD: 16.23

ClinVar Submissions (2)

- Ciliary dyskinesia

  ### Ciliary dyskinesia

  Primary ciliary dyskinesia (PCD) is associated with situs abnormalities, abnormal sperm motility, and abnormal ciliary structure and function that result in retention of mucus and bacteria in the respiratory tract leading to chronic otosinopulmonary disease. More than 75% of full-term neonates with PCD have "neonatal respiratory distress" requiring supplemental oxygen for days to weeks. Chronic airway infection, apparent in early childhood, results in bronchiectasis that is almost uniformly present in adulthood. Nasal congestion and sinus infections, apparent in early childhood, persist through adulthood. Chronic/recurrent ear infection, apparent in most young children, can be associated with transient or later irreversible hearing loss. Situs inversus totalis (mirror-image reversal of all visceral organs with no apparent physiologic consequences) is present in 40%-50% of individuals with PCD; heterotaxy (discordance of right and left patterns of ordinarily asymmetric structures that can be associated with significant malformations) is present in approximately 12%. Virtually all males with PCD are infertile as a result of abnormal sperm motility.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 07, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 2:26456494

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 07, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 2:26456494

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: ADA
Variant: c.22G>A
(p.Asp8Asn)
rsID: rs73598374
Ref Allele: C
Alt Allele: T
Freq: 4.1515%uncommon
CADD: 19.31

ClinVar Submissions (3)

- Adenosine deaminase 2 allozyme

  ### Adenosine deaminase 2 allozyme

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 13, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 20:44651586
  OMIM Allelic Variant: 608958.0021

- Severe combined immunodeficiency due to ADA deficiency

  ### Severe combined immunodeficiency due to ADA deficiency

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 13, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 20:44651586
  OMIM Allelic Variant: 608958.0021

- not specified

  ### not specified

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 13, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 3
  Clinical Significance: Conflicting interpretations of pathogenicity
  Assembly: GRCh38
  Chromosome/Position: 20:44651586
  OMIM Allelic Variant: 608958.0021

Low clinical importance, Likely benign — This common variant is reported to reduce adenosine deaminase enzyme activity. It has been associated with an increased tendency for non-REM sleep -- more slow wave sleep, less nocturnal wakings, and a stronger negative impact of sleep deprivation. A role for this gene and variant was previously proposed for autism susceptibility, but this is controversial and was not replicated by later studies.

Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (10)

Homo

TT

Gene: ARHGAP31
Variant: c.*1156C>G
rsID: rs115630304
Ref Allele: C
Alt Allele: G
Freq: 4.1635%uncommon
CADD: 0.395

ClinVar Submissions (1)

- Adams-Oliver syndrome

  ### Adams-Oliver syndrome

  Adams-Oliver syndrome (AOS) is characterized by aplasia cutis congenita (ACC) of the scalp and terminal transverse limb defects (TTLD). ACC lesions usually occur in the midline of the parietal or occipital regions, but can also occur on the abdomen or limbs. At birth, an ACC lesion may already have the appearance of a healed scar. ACC lesions less than 5 cm often involve only the skin and almost always heal over a period of months; larger lesions are more likely to involve the skull and possibly the dura, and are at greater risk for complications, which can include infection, hemorrhage, or thrombosis, and can result in death. The limb defects range from mild (unilateral or bilateral short distal phalanges) to severe (complete absence of all toes or fingers, feet or hands, or more, often resembling an amputation). The lower extremities are almost always more severely affected than the upper extremities. Additional major features frequently include cardiovascular malformations/dysfunction (23%), brain anomalies, and less frequently renal, liver, and eye anomalies.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 3:119417420

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CG

Gene: ARHGAP31
Variant: c.*1176T>G
rsID: rs114261128
Ref Allele: T
Alt Allele: G
Freq: 4.1635%uncommon
CADD: 1.23

ClinVar Submissions (1)

- Adams-Oliver syndrome

  ### Adams-Oliver syndrome

  Adams-Oliver syndrome (AOS) is characterized by aplasia cutis congenita (ACC) of the scalp and terminal transverse limb defects (TTLD). ACC lesions usually occur in the midline of the parietal or occipital regions, but can also occur on the abdomen or limbs. At birth, an ACC lesion may already have the appearance of a healed scar. ACC lesions less than 5 cm often involve only the skin and almost always heal over a period of months; larger lesions are more likely to involve the skull and possibly the dura, and are at greater risk for complications, which can include infection, hemorrhage, or thrombosis, and can result in death. The limb defects range from mild (unilateral or bilateral short distal phalanges) to severe (complete absence of all toes or fingers, feet or hands, or more, often resembling an amputation). The lower extremities are almost always more severely affected than the upper extremities. Additional major features frequently include cardiovascular malformations/dysfunction (23%), brain anomalies, and less frequently renal, liver, and eye anomalies.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 3:119417440

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

TG

Gene: SLC12A5
Variant: c.1150C>G
(p.Pro384Ala)
rsID: rs16985442
Ref Allele: C
Alt Allele: G
Freq: 4.1738%uncommon
CADD: 7.242

ClinVar Submissions (1)

- Early infantile epileptic encephalopathy 34, Autosomal recessive

  ### Early infantile epileptic encephalopathy 34

  SLC12A5-related epilepsy of infancy with migrating focal seizures (SLC12A5-EIMFS), reported to date in nine children, is characterized by onset of seizures before age six months and either developmental delay or developmental regression with seizure onset. Of these nine children, six had severe developmental delay with no progress of abilities and three made notable neurodevelopmental progress. Eight had postnatal microcephaly and hypotonia. In most children epilepsy begins as focal motor seizures (typically involving head and eye deviation) that become multifocal and intractable to conventional antiepileptic drugs (AEDs).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 14, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 20:46043236

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CG

Gene: LPA
Variant: c.3947+467T>C
rsID: rs10455872
Ref Allele: A
Alt Allele: G
Freq: 4.1762%uncommon
CADD: 0.033

ClinVar Submissions (1)

- hmg coa reductase inhibitors response - Efficacy, Toxicity/ADR

  ### hmg coa reductase inhibitors response - Efficacy, Toxicity/ADR

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 08, 2018
  Review Status: reviewed by expert panel
  Number of Submitters: 1
  Clinical Significance: drug response
  Assembly: GRCh38
  Chromosome/Position: 6:160589086

Expert Reviewed drug response

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (62)

Hetero

AG

Gene: SLC5A1
Variant: c.1899G>A
(p.Thr633=)
rsID: rs33943816
Ref Allele: G
Alt Allele: A
Freq: 4.1802%uncommon
CADD: 0.107

ClinVar Submissions (2)

- Congenital glucose-galactose malabsorption, Autosomal recessive

  ### Congenital glucose-galactose malabsorption

  Glucose/galactose malabsorption (GGM) is a rare autosomal recessive disorder caused by a defect in glucose and galactose transport across the intestinal brush border. Patients with GGM present with neonatal onset of severe life-threatening watery diarrhea and dehydration. If diagnosed and treated properly, patients can fully recover and show normal growth and development (summary by Xin and Wang, 2011).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 22:32110117

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 22:32110117

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: CASP10
Variant: c.1228G>A
(p.Val410Ile)
rsID: rs13010627
Ref Allele: G
Alt Allele: A
Freq: 4.1906%uncommon
CADD: 15.67

ClinVar Submissions (2)

- Autoimmune lymphoproliferative syndrome, Autosomal dominant

  ### Autoimmune lymphoproliferative syndrome

  Autoimmune lymphoproliferative syndrome (ALPS), caused by defective lymphocyte homeostasis, is characterized by the following: Non-malignant lymphoproliferation (lymphadenopathy, hepatosplenomegaly with or without hypersplenism) that often improves with age. Autoimmune disease, mostly directed toward blood cells. Lifelong increased risk for both Hodgkin and non-Hodgkin lymphoma. In ALPS-FAS (the most common and best-characterized type of ALPS, associated with heterozygous germline pathogenic variants in FAS), non-malignant lymphoproliferation typically manifests in the first years of life, inexplicably waxes and wanes, and then often decreases without treatment in the second decade of life; in many affected individuals, however, neither splenomegaly nor the overall expansion of lymphocyte subsets in peripheral blood decreases. Although autoimmunity is often not present at the time of diagnosis or at the time of the most extensive lymphoproliferation, autoantibodies can be detected before autoimmune disease manifests clinically. In ALPS-FAS caused by homozygous or compound heterozygous (biallelic) pathogenic variants in FAS, severe lymphoproliferation occurs before, at, or shortly after birth, and usually results in death at an early age. ALPS-sFAS, resulting from somatic FAS pathogenic variants in selected cell populations, notably the alpha/beta double-negative T cells (a/ß-DNT cells), appears to be similar to ALPS-FAS resulting from heterozygous germline pathogenic variants in FAS, although lower incidence of splenectomy and lower lymphocyte counts have been reported in ALPS-sFAS and no cases of lymphoma have yet been published.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 02, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:201209375

- Autoimmune lymphoproliferative syndrome type 2

  ### Autoimmune lymphoproliferative syndrome type 2

  A rare, primary immunodeficiency with an autosomal dominant pattern of inheritance but incomplete penetrance. It is caused by a mutation in the CASP10 (caspase-10) gene that leads to defective Fas-induced apoptosis. Disruption of Fas-induced apoptosis impairs lymphocyte homeostasis and immune tolerance. Characteristic laboratory findings include an increase in circulating, double-negative (CD4-/CD8-) T cells in the setting of immune-mediated anemia, thrombocytopenia and neutropenia. Clinical signs present in childhood include fatigue, pallor, bruising, hepatosplenomegaly and chronic, non-malignant, non-infectious lymphadenopathy. The clinical course is influenced by a strong association with other autoimmune disorders and an increased risk for developing Hodgkin and non-Hodgkin lymphoma.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 02, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:201209375

- Autoimmune lymphoproliferative syndrome, type 2A, Autosomal dominant

  ### Autoimmune lymphoproliferative syndrome, type 2A

  Autoimmune lymphoproliferative syndrome (ALPS), caused by defective lymphocyte homeostasis, is characterized by the following: Non-malignant lymphoproliferation (lymphadenopathy, hepatosplenomegaly with or without hypersplenism) that often improves with age. Autoimmune disease, mostly directed toward blood cells. Lifelong increased risk for both Hodgkin and non-Hodgkin lymphoma. In ALPS-FAS (the most common and best-characterized type of ALPS, associated with heterozygous germline pathogenic variants in FAS), non-malignant lymphoproliferation typically manifests in the first years of life, inexplicably waxes and wanes, and then often decreases without treatment in the second decade of life; in many affected individuals, however, neither splenomegaly nor the overall expansion of lymphocyte subsets in peripheral blood decreases. Although autoimmunity is often not present at the time of diagnosis or at the time of the most extensive lymphoproliferation, autoantibodies can be detected before autoimmune disease manifests clinically. In ALPS-FAS caused by homozygous or compound heterozygous (biallelic) pathogenic variants in FAS, severe lymphoproliferation occurs before, at, or shortly after birth, and usually results in death at an early age. ALPS-sFAS, resulting from somatic FAS pathogenic variants in selected cell populations, notably the alpha/beta double-negative T cells (a/ß-DNT cells), appears to be similar to ALPS-FAS resulting from heterozygous germline pathogenic variants in FAS, although lower incidence of splenectomy and lower lymphocyte counts have been reported in ALPS-sFAS and no cases of lymphoma have yet been published.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 02, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:201209375

Low clinical importance, Likely protective — Reported to have a protective effect on breast cancer. If the lifetime risk of breast cancer is 12%, women with this variant may have a lower risk of 8-9% (30% less than average).

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (8)

Hetero

GA

Gene: OTOF
Variant: c.5655C>T
(p.Arg1885=)
rsID: rs45442103
Ref Allele: G
Alt Allele: A
Freq: 4.2256%uncommon
CADD: 14.03

ClinVar Submissions (5)

- Deafness, autosomal recessive 9, Autosomal recessive

  ### Deafness, autosomal recessive 9

  OTOF-related deafness (DFNB9 nonsyndromic hearing loss) is characterized by two phenotypes: prelingual nonsyndromic hearing loss and, less frequently, temperature-sensitive nonsyndromic auditory neuropathy (TS-NSAN). The nonsyndromic hearing loss is bilateral severe-to-profound congenital deafness. In the first one or two years of life, OTOF-related deafness can appear to be an auditory neuropathy based on electrophysiologic testing in which auditory brain stem responses (ABRs) are absent and otoacoustic emissions (OAEs) are present. However, with time OAEs disappear and electrophysiologic testing is more consistent with a cochlear defect. The distinction between auditory neuropathy and a cochlear defect is important as cochlear implants may be of marginal value in persons with auditory neuropathy but have been shown to be effective for individuals with OTOF-related deafness. TS-NSAN is characterized by normal-to-mild hearing loss in the absence of fever and significant hearing loss ranging from severe to profound in the presence of fever. When the fever resolves, hearing returns to normal.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 10, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 2:26460909

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 10, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 2:26460909

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 10, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 2:26460909

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (3)

Hetero

GA

Gene: GRM6
Variant: c.2397C>T
(p.Phe799=)
rsID: rs17078875
Ref Allele: G
Alt Allele: A
Freq: 4.2336%uncommon
CADD: 21.6

ClinVar Submissions (1)

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: no assertion provided
  Number of Submitters: 1
  Clinical Significance: not provided
  Assembly: GRCh38
  Chromosome/Position: 5:178982949

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: P3H1
Variant: c.139G>T
(p.Ala47Ser)
rsID: rs55716016
Ref Allele: C
Alt Allele: A
Freq: 4.2352%uncommon
CADD: 16.17

ClinVar Submissions (3)

- Osteogenesis imperfecta type 8, Autosomal recessive

  ### Osteogenesis imperfecta type 8

  Osteogenesis imperfecta (OI) is a connective tissue disorder characterized by bone fragility and low bone mass. Due to considerable phenotypic variability, Sillence et al. (1979) developed a classification of OI subtypes based on clinical features and disease severity: OI type I, with blue sclerae (166200); perinatal lethal OI type II, also known as congenital OI (166210); OI type III, a progressively deforming form with normal sclerae (259420); and OI type IV, with normal sclerae (166220). Most forms of OI are autosomal dominant with mutations in one of the 2 genes that code for type I collagen alpha chains, COL1A1 (120150) and COL1A2 (120160). Cabral et al. (2007) described a form of autosomal recessive OI, which they designated OI type VIII, characterized by white sclerae, severe growth deficiency, extreme skeletal undermineralization, and bulbous metaphyses.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 01, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 1:42766833

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 01, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 1:42766833

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 01, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 1:42766833

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CA

Gene: TPM1
Variant: c.486T>C
(p.Tyr162=)
rsID: rs11558747
Ref Allele: T
Alt Allele: C
Freq: 4.2383%uncommon
CADD: 11.81

ClinVar Submissions (7)

- Cardiovascular phenotype

  ### Cardiovascular phenotype

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 23, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 15:63059674

- Dilated Cardiomyopathy, Dominant

  ### Dilated Cardiomyopathy, Dominant

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 23, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 15:63059674

- Hypertrophic cardiomyopathy

  ### Hypertrophic cardiomyopathy

  A condition in which the myocardium is hypertrophied without an obvious cause. The hypertrophy is generally asymmetric and may be associated with obstruction of the ventricular outflow tract.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 23, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 15:63059674

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 23, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 15:63059674

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 23, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 7
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 15:63059674

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (6)

Hetero

TC

Gene: CHD7
Variant: c.7356A>G
(p.Thr2452=)
rsID: rs2272727
Ref Allele: A
Alt Allele: G
Freq: 4.2606%uncommon
CADD: 8.237

ClinVar Submissions (9)

- CHARGE association, Autosomal dominant

  ### CHARGE association

  CHARGE is a mnemonic for coloboma, heart defects, choanal atresia, retarded growth and development, genital abnormalities, and ear anomalies. CHARGE syndrome is characterized by the following: Unilateral or bilateral coloboma of the iris, retina-choroid, and/or disc with or without microphthalmos (80%-90% of individuals). Unilateral or bilateral choanal atresia or stenosis (50%-60%). Cranial nerve dysfunction resulting in hyposmia or anosmia, unilateral or bilateral facial palsy (40%), impaired hearing, and/or swallowing problems (70%-90%). Abnormal outer ears, ossicular malformations, Mondini defect of the cochlea and absent or hypoplastic semicircular canals (>90%). Cryptorchidism in males and hypogonadotropic hypogonadism in both males and females. Developmental delay. Cardiovascular malformations (75%-85%). Growth deficiency (70%-80%). Orofacial clefts (15%-20%). Tracheoesophageal fistula (15%-20%). Neonates with CHARGE syndrome often have multiple life-threatening medical conditions. Feeding difficulties are a major cause of morbidity in all age groups.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 23, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 8:60856636

- History of neurodevelopmental disorder

  ### History of neurodevelopmental disorder

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 23, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 8:60856636

- Hypogonadism with anosmia

  ### Hypogonadism with anosmia

  Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) is characterized by inappropriately low serum concentrations of the gonadotropins LH (luteinizing hormone) and FSH (follicle-stimulating hormone) in the presence of low circulating concentrations of sex steroids. IGD is associated with a normal sense of smell (normosmic IGD) in approximately 40% of affected individuals and an impaired sense of smell (Kallmann syndrome) in approximately 60%. IGD can first become apparent in infancy, adolescence, or adulthood. Infant boys with congenital IGD often have micropenis and cryptorchidism. Adolescents and adults with IGD have clinical evidence of hypogonadism and incomplete sexual maturation on physical examination. Adult males with IGD tend to have prepubertal testicular volume (i.e., <4 mL), absence of secondary sexual features (e.g., facial and axillary hair growth, deepening of the voice), decreased muscle mass, diminished libido, erectile dysfunction, and infertility. Adult females have little or no breast development and primary amenorrhea. Although skeletal maturation is delayed, the rate of linear growth is usually normal except for the absence of a distinct pubertal growth spurt.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 23, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 8:60856636

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 23, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 8:60856636

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 23, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 8:60856636

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (4)

Hetero

AG

Gene: GHSR
Variant: c.*1024G>C
rsID: rs9880206
Ref Allele: C
Alt Allele: G
Freq: 4.2814%uncommon
CADD: 0.025

ClinVar Submissions (1)

- Short stature, idiopathic, autosomal, Autosomal dominant

  ### Short stature, idiopathic, autosomal

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 3:172444137

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CG

Gene: HAND1
Variant: c.468T>G
(p.Ser156=)
rsID: rs34402828
Ref Allele: A
Alt Allele: C
Freq: 4.2821%uncommon
CADD: 13.12

ClinVar Submissions (1)

- Hypoplastic left heart syndrome

  ### Hypoplastic left heart syndrome

  Critical congenital heart disease (CCHD) is a term that refers to a group of serious heart defects that are present from birth. These abnormalities result from problems with the formation of one or more parts of the heart during the early stages of embryonic development. CCHD prevents the heart from pumping blood effectively or reduces the amount of oxygen in the blood. As a result, organs and tissues throughout the body do not receive enough oxygen, which can lead to organ damage and life-threatening complications. Individuals with CCHD usually require surgery soon after birth.Although babies with CCHD may appear healthy for the first few hours or days of life, signs and symptoms soon become apparent. These can include an abnormal heart sound during a heartbeat (heart murmur), rapid breathing (tachypnea), low blood pressure (hypotension), low levels of oxygen in the blood (hypoxemia), and a blue or purple tint to the skin caused by a shortage of oxygen (cyanosis). If untreated, CCHD can lead to shock, coma, and death. However, most people with CCHD now survive past infancy due to improvements in early detection, diagnosis, and treatment.Some people with treated CCHD have few related health problems later in life. However, long-term effects of CCHD can include delayed development and reduced stamina during exercise. Adults with these heart defects have an increased risk of abnormal heart rhythms, heart failure, sudden cardiac arrest, stroke, and premature death.Each of the heart defects associated with CCHD affects the flow of blood into, out of, or through the heart. Some of the heart defects involve structures within the heart itself, such as the two lower chambers of the heart (the ventricles) or the valves that control blood flow through the heart. Others affect the structure of the large blood vessels leading into and out of the heart (including the aorta and pulmonary artery). Still others involve a combination of these structural abnormalities.People with CCHD have one or more specific heart defects. The heart defects classified as CCHD include coarctation of the aorta, double-outlet right ventricle, D-transposition of the great arteries, Ebstein anomaly, hypoplastic left heart syndrome, interrupted aortic arch, pulmonary atresia with intact septum, single ventricle, total anomalous pulmonary venous connection, tetralogy of Fallot, tricuspid atresia, and truncus arteriosus.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 10, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 5:154477541

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

AC

Gene: KMT2D
Variant: c.10671A>G
(p.Pro3557=)
rsID: rs61942218
Ref Allele: T
Alt Allele: C
Freq: 4.2877%uncommon
CADD: 3.223

ClinVar Submissions (5)

- Kabuki syndrome, Autosomal dominant

  ### Kabuki syndrome

  Kabuki syndrome is a disorder that affects many parts of the body. It is characterized by distinctive facial features including arched eyebrows; long eyelashes; long openings of the eyelids (long palpebral fissures) with the lower lids turned out (everted) at the outside edges; a flat, broadened tip of the nose; and large protruding earlobes. The name of this disorder comes from the resemblance of its characteristic facial appearance to stage makeup used in traditional Japanese Kabuki theater.People with Kabuki syndrome have mild to severe developmental delay and intellectual disability. Affected individuals may also have seizures, an unusually small head size (microcephaly), or weak muscle tone (hypotonia). Some have eye problems such as rapid, involuntary eye movements (nystagmus) or eyes that do not look in the same direction (strabismus).Other characteristic features of Kabuki syndrome include short stature and skeletal abnormalities such as abnormal side-to-side curvature of the spine (scoliosis), short fifth (pinky) fingers, or problems with the hip and knee joints. The roof of the mouth may have an abnormal opening (cleft palate) or be high and arched, and dental problems are common in affected individuals. People with Kabuki syndrome may also have fingerprints with unusual features and fleshy pads at the tips of the fingers. These prominent finger pads are called fetal finger pads because they normally occur in human fetuses; in most people they disappear before birth.A wide variety of other health problems occur in some people with Kabuki syndrome. Among the most commonly reported are heart abnormalities, frequent ear infections (otitis media), hearing loss, and early puberty.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 01, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 12:49034136

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 01, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 12:49034136

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (3)

Hetero

TC

Gene: TSC2
Variant: c.976-63G>A
rsID: rs12927333
Ref Allele: G
Alt Allele: A
Freq: 4.2909%uncommon
CADD: 3.215

ClinVar Submissions (1)

- Tuberous sclerosis syndrome

  ### Tuberous sclerosis syndrome

  Tuberous sclerosis complex (TSC) involves abnormalities of the skin (hypomelanotic macules, confetti skin lesions, facial angiofibromas, shagreen patches, fibrous cephalic plaques, ungual fibromas); brain (subependymal nodules, cortical dysplasias, and subependymal giant cell astrocytomas [SEGAs], seizures, intellectual disability / developmental delay, psychiatric illness); kidney (angiomyolipomas, cysts, renal cell carcinomas); heart (rhabdomyomas, arrhythmias); and lungs (lymphangioleiomyomatosis [LAM], multifocal micronodular pneumonocyte hyperplasia). Central nervous system tumors are the leading cause of morbidity and mortality; renal disease is the second leading cause of early death.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: no assertion provided
  Number of Submitters: 1
  Clinical Significance: not provided
  Assembly: GRCh38
  Chromosome/Position: 16:2060607

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: TSC2
Variant: c.3884-56C>G
rsID: rs1800724
Ref Allele: C
Alt Allele: G
Freq: 4.3212%uncommon
CADD: 4.672

ClinVar Submissions (1)

- Tuberous sclerosis syndrome

  ### Tuberous sclerosis syndrome

  Tuberous sclerosis complex (TSC) involves abnormalities of the skin (hypomelanotic macules, confetti skin lesions, facial angiofibromas, shagreen patches, fibrous cephalic plaques, ungual fibromas); brain (subependymal nodules, cortical dysplasias, and subependymal giant cell astrocytomas [SEGAs], seizures, intellectual disability / developmental delay, psychiatric illness); kidney (angiomyolipomas, cysts, renal cell carcinomas); heart (rhabdomyomas, arrhythmias); and lungs (lymphangioleiomyomatosis [LAM], multifocal micronodular pneumonocyte hyperplasia). Central nervous system tumors are the leading cause of morbidity and mortality; renal disease is the second leading cause of early death.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: no assertion provided
  Number of Submitters: 1
  Clinical Significance: not provided
  Assembly: GRCh38
  Chromosome/Position: 16:2083639

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (2)

Hetero

CG

Gene: TSC2
Variant: c.1578C>T
(p.Ser526=)
rsID: rs34012042
Ref Allele: C
Alt Allele: T
Freq: 4.3283%uncommon
CADD: 6.021

ClinVar Submissions (9)

- Hereditary cancer-predisposing syndrome

  ### Hereditary cancer-predisposing syndrome

  The condition of a pattern of malignancies within a family, but not every individual's necessarily having the same neoplasm. Characteristically the tumor tends to occur at an earlier than average age, individuals may have more than one primary tumor, the tumors may be multicentric, usually more than 25 percent of the individuals in direct lineal descent from the proband are affected, and the cancer predisposition in these families behaves as an autosomal dominant trait with about 60 percent penetrance.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 14, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 16:2064406

- Lymphangiomyomatosis

  ### Lymphangiomyomatosis

  Lymphangioleiomyomatosis (LAM) is a condition that affects the lungs, the kidneys, and the lymphatic system. The lymphatic system consists of a network of vessels that transport lymph fluid and immune cells throughout the body. Lymph fluid helps exchange immune cells, proteins, and other substances between the blood and tissues.LAM is found almost exclusively in women. It often occurs as a feature of an inherited syndrome called tuberous sclerosis complex. When LAM occurs alone it is called isolated or sporadic LAM.Signs and symptoms of LAM most often appear during a woman's thirties. Affected women have an overgrowth of abnormal smooth muscle-like cells (LAM cells) in the lungs, resulting in the formation of lung cysts and the destruction of normal lung tissue. They may also have an accumulation of fluid in the cavity around the lungs (chylothorax).The lung abnormalities resulting from LAM may cause difficulty breathing (dyspnea), chest pain, and coughing, which may bring up blood (hemoptysis). Many women with this disorder have recurrent episodes of collapsed lung (spontaneous pneumothorax). The lung problems may be progressive and, without lung transplantation, may eventually lead to limitations in activities of daily living, the need for oxygen therapy, and respiratory failure. Although LAM cells are not considered cancerous, they may spread between tissues (metastasize). As a result, the condition may recur even after lung transplantation.Women with LAM may develop cysts in the lymphatic vessels of the chest and abdomen. These cysts are called lymphangioleiomyomas. Affected women may also develop tumors called angiomyolipomas made up of LAM cells, fat cells, and blood vessels. Angiomyolipomas usually develop in the kidneys. Internal bleeding is a common complication of angiomyolipomas.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 14, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 16:2064406

- Lymphangiomyomatosis

  ### Lymphangiomyomatosis

  Lymphangioleiomyomatosis (LAM) is a condition that affects the lungs, the kidneys, and the lymphatic system. The lymphatic system consists of a network of vessels that transport lymph fluid and immune cells throughout the body. Lymph fluid helps exchange immune cells, proteins, and other substances between the blood and tissues.LAM is found almost exclusively in women. It often occurs as a feature of an inherited syndrome called tuberous sclerosis complex. When LAM occurs alone it is called isolated or sporadic LAM.Signs and symptoms of LAM most often appear during a woman's thirties. Affected women have an overgrowth of abnormal smooth muscle-like cells (LAM cells) in the lungs, resulting in the formation of lung cysts and the destruction of normal lung tissue. They may also have an accumulation of fluid in the cavity around the lungs (chylothorax).The lung abnormalities resulting from LAM may cause difficulty breathing (dyspnea), chest pain, and coughing, which may bring up blood (hemoptysis). Many women with this disorder have recurrent episodes of collapsed lung (spontaneous pneumothorax). The lung problems may be progressive and, without lung transplantation, may eventually lead to limitations in activities of daily living, the need for oxygen therapy, and respiratory failure. Although LAM cells are not considered cancerous, they may spread between tissues (metastasize). As a result, the condition may recur even after lung transplantation.Women with LAM may develop cysts in the lymphatic vessels of the chest and abdomen. These cysts are called lymphangioleiomyomas. Affected women may also develop tumors called angiomyolipomas made up of LAM cells, fat cells, and blood vessels. Angiomyolipomas usually develop in the kidneys. Internal bleeding is a common complication of angiomyolipomas.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 14, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 16:2064406

- Tuberous sclerosis 2, Autosomal dominant

  ### Tuberous sclerosis 2

  Tuberous sclerosis complex (TSC) involves abnormalities of the skin (hypomelanotic macules, confetti skin lesions, facial angiofibromas, shagreen patches, fibrous cephalic plaques, ungual fibromas); brain (subependymal nodules, cortical dysplasias, and subependymal giant cell astrocytomas [SEGAs], seizures, intellectual disability / developmental delay, psychiatric illness); kidney (angiomyolipomas, cysts, renal cell carcinomas); heart (rhabdomyomas, arrhythmias); and lungs (lymphangioleiomyomatosis [LAM], multifocal micronodular pneumonocyte hyperplasia). Central nervous system tumors are the leading cause of morbidity and mortality; renal disease is the second leading cause of early death.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 14, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 16:2064406

- Tuberous sclerosis syndrome

  ### Tuberous sclerosis syndrome

  Tuberous sclerosis complex (TSC) involves abnormalities of the skin (hypomelanotic macules, confetti skin lesions, facial angiofibromas, shagreen patches, fibrous cephalic plaques, ungual fibromas); brain (subependymal nodules, cortical dysplasias, and subependymal giant cell astrocytomas [SEGAs], seizures, intellectual disability / developmental delay, psychiatric illness); kidney (angiomyolipomas, cysts, renal cell carcinomas); heart (rhabdomyomas, arrhythmias); and lungs (lymphangioleiomyomatosis [LAM], multifocal micronodular pneumonocyte hyperplasia). Central nervous system tumors are the leading cause of morbidity and mortality; renal disease is the second leading cause of early death.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 14, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 16:2064406

- Tuberous sclerosis syndrome

  ### Tuberous sclerosis syndrome

  Tuberous sclerosis complex (TSC) involves abnormalities of the skin (hypomelanotic macules, confetti skin lesions, facial angiofibromas, shagreen patches, fibrous cephalic plaques, ungual fibromas); brain (subependymal nodules, cortical dysplasias, and subependymal giant cell astrocytomas [SEGAs], seizures, intellectual disability / developmental delay, psychiatric illness); kidney (angiomyolipomas, cysts, renal cell carcinomas); heart (rhabdomyomas, arrhythmias); and lungs (lymphangioleiomyomatosis [LAM], multifocal micronodular pneumonocyte hyperplasia). Central nervous system tumors are the leading cause of morbidity and mortality; renal disease is the second leading cause of early death.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 14, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 16:2064406

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 14, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 16:2064406

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 14, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 9
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 16:2064406

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (8)

Hetero

CT

Gene: DOCK2
Variant: c.2352A>G
(p.Gln784=)
rsID: rs13155521
Ref Allele: A
Alt Allele: G
Freq: 4.3411%uncommon
CADD: 2.885

ClinVar Submissions (1)

- Immunodeficiency 40, Autosomal recessive

  ### Immunodeficiency 40

  Immunodeficiency-40 is an autosomal recessive primary form of combined immunodeficiency mainly affecting T-cell number and function, with other more variable defects in B-cell and NK-cell function. Patients have onset of severe invasive bacterial and viral infections in early childhood and may die without bone marrow transplantation (summary by Dobbs et al., 2015).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 21, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 5:169747480

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

AG

Gene: DIS3L2
Variant: c.2187C>T
(p.Pro729=)
rsID: rs75782436
Ref Allele: C
Alt Allele: T
Freq: 4.361%uncommon
CADD: 0.121

ClinVar Submissions (2)

- Renal hamartomas nephroblastomatosis and fetal gigantism, Autosomal recessive

  ### Renal hamartomas nephroblastomatosis and fetal gigantism

  Perlman syndrome is an autosomal recessive congenital overgrowth syndrome with similarities to Beckwith-Wiedemann syndrome (BWS; 130650). Affected children are large at birth, are hypotonic, and show organomegaly, characteristic facial dysmorphisms (inverted V-shaped upper lip, prominent forehead, deep-set eyes, broad and flat nasal bridge, and low-set ears), renal anomalies (nephromegaly and hydronephrosis), frequent neurodevelopmental delay, and high neonatal mortality. Perlman syndrome is associated with a high risk of Wilms tumor, with a 64% incidence in infants surviving beyond the neonatal period. The tumor is diagnosed at an earlier age in these individuals compared with sporadic cases (less than 2 years and 3-4 years of age, respectively), and there is a high frequency of bilateral tumors (55%). Histologic examination of the kidneys in children with Perlman syndrome shows frequent nephroblastomatosis, which is a precursor lesion for Wilms tumor (summary by Astuti et al., 2012).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 09, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:232334397

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CT

Gene: TRPC6
Variant: c.2115C>T
(p.Tyr705=)
rsID: rs61743044
Ref Allele: G
Alt Allele: A
Freq: 4.3634%uncommon
CADD: 0.109

ClinVar Submissions (3)

- Focal segmental glomerulosclerosis

  ### Focal segmental glomerulosclerosis

  A clinicopathological syndrome or diagnostic term for a type of glomerular injury that has multiple causes, primary or secondary. Clinical features include PROTEINURIA, reduced GLOMERULAR FILTRATION RATE, and EDEMA. Kidney biopsy initially indicates focal segmental glomerular consolidation (hyalinosis) or scarring which can progress to globally sclerotic glomeruli leading to eventual KIDNEY FAILURE.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 15, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 11:101472227

- Focal segmental glomerulosclerosis 2

  ### Focal segmental glomerulosclerosis 2

  Focal segmental glomerulosclerosis (FSGS) is a pathologic entity associated clinically with proteinuria, the nephrotic syndrome (NPHS), and progressive loss of renal function. It is a common cause of end-stage renal disease (ESRD) (review by Meyrier, 2005). For a general phenotypic description and a discussion of genetic heterogeneity of focal segmental glomerulosclerosis and nephrotic syndrome (NPHS), see FSGS1 (603278).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 15, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 11:101472227

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: May 15, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 11:101472227

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (2)

Hetero

GA

Gene: ABAT
Variant: c.*298C>T
rsID: rs737694
Ref Allele: C
Alt Allele: T
Freq: 4.3785%uncommon
CADD: 6.341

ClinVar Submissions (1)

- Gamma-aminobutyric acid transaminase deficiency, Autosomal recessive

  ### Gamma-aminobutyric acid transaminase deficiency

  GABA-transaminase deficiency is characterized by neonatal or early infantile-onset encephalopathy, hypotonia, hypersomnolence, epilepsy, choreoathetosis, and accelerated linear growth. Electroencephalograms show burst-suppression, modified hypsarrhythmia, multifocal spikes, and generalized spike-wave. Severity varies, but most patients have profound developmental impairment and some patients die in infancy (summary by Koenig et al., 2017).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 16:8781728

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CT

Gene: DHDDS
Variant: c.*629C>T
rsID: rs2494394
Ref Allele: C
Alt Allele: T
Freq: 4.4151%uncommon
CADD: 17.19

ClinVar Submissions (1)

- Retinitis Pigmentosa, Recessive

  ### Retinitis Pigmentosa, Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Uncertain significance
  Assembly: GRCh38
  Chromosome/Position: 1:26469760

Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CT

Gene: MTHFR
Variant: c.1781G>A
(p.Arg594Gln)
rsID: rs2274976
Ref Allele: C
Alt Allele: T
Freq: 4.4239%uncommon
CADD: 14.31

ClinVar Submissions (5)

- Neural tube defects, folate-sensitive

  ### Neural tube defects, folate-sensitive

  Neural tube defects have a birth incidence of approximately 1 in 1,000 in American Caucasians and are the second most common type of birth defect after congenital heart defects. The most common NTDs are open spina bifida (myelomeningocele) and anencephaly (206500) (Detrait et al., 2005). Women with elevated plasma homocysteine, low folate, or low vitamin B12 (cobalamin) are at increased risk of having a child with a neural tube defect (O'Leary et al., 2005). Motulsky (1996) cited evidence from the Centers for Disease Control ( Anonymous, 1992) that folic acid given before and during the first 4 weeks of pregnancy can prevent 50% or more of neural tube defects. Botto et al. (1999) and Detrait et al. (2005) provided reviews of neural tube defects. De Marco et al. (2006) provided a detailed review of neurulation and the possible etiologies of neural tube defects.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 13, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign, other
  Assembly: GRCh38
  Chromosome/Position: 1:11790870

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 13, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign, other
  Assembly: GRCh38
  Chromosome/Position: 1:11790870

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jan 13, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign, other
  Assembly: GRCh38
  Chromosome/Position: 1:11790870

Benign/Likely benign, other

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (36)

Hetero

CT

Gene: SLC12A5
Variant: c.1512G>A
(p.Thr504=)
rsID: rs41282782
Ref Allele: G
Alt Allele: A
Freq: 4.4263%uncommon
CADD: 8.452

ClinVar Submissions (1)

- Early infantile epileptic encephalopathy 34, Autosomal recessive

  ### Early infantile epileptic encephalopathy 34

  SLC12A5-related epilepsy of infancy with migrating focal seizures (SLC12A5-EIMFS), reported to date in nine children, is characterized by onset of seizures before age six months and either developmental delay or developmental regression with seizure onset. Of these nine children, six had severe developmental delay with no progress of abilities and three made notable neurodevelopmental progress. Eight had postnatal microcephaly and hypotonia. In most children epilepsy begins as focal motor seizures (typically involving head and eye deviation) that become multifocal and intractable to conventional antiepileptic drugs (AEDs).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 14, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 20:46045083

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

GA

Gene: SURF1
Variant: c.280T>C
(p.Leu94=)
rsID: rs28615629
Ref Allele: A
Alt Allele: G
Freq: 4.447%uncommon
CADD: 17.12

ClinVar Submissions (4)

- Leigh syndrome, Autosomal recessive

  ### Leigh syndrome

  Leigh syndrome is a clinically and genetically heterogeneous disorder resulting from defective mitochondrial energy generation. It most commonly presents as a progressive and severe neurodegenerative disorder with onset within the first months or years of life, and may result in early death. Affected individuals usually show global developmental delay or developmental regression, hypotonia, ataxia, dystonia, and ophthalmologic abnormalities, such as nystagmus or optic atrophy. The neurologic features are associated with the classic findings of T2-weighted hyperintensities in the basal ganglia and/or brainstem on brain imaging. Leigh syndrome can also have detrimental multisystemic affects on the cardiac, hepatic, gastrointestinal, and renal organs. Biochemical studies in patients with Leigh syndrome tend to show increased lactate and abnormalities of mitochondrial oxidative phosphorylation. Thus, Leigh syndrome may be a clinical feature of a primary deficiency of any of the mitochondrial respiratory chain complexes: complex I deficiency (see 252010), complex II deficiency (see 252011), complex III deficiency (see 124000), complex IV deficiency (cytochrome c oxidase; see 220110), or complex V deficiency (see 604273) (summary by Lake et al., 2015). Genetic Heterogeneity of Leigh Syndrome Mutations in complex I genes include mitochondrial-encoded MTND2 (516001), MTND3 (516002), MTND5 (516005), and MTND6 (516006), the nuclear-encoded NDUFS1 (157655), NDUFS3 (603846), NDUFS4 (602694), NDUFS7 (601825), NDUFS8 (602141), NDUFA2 (602137), NDUFA9 (603834), NDUFA10 (603835), NDUFA12 (614530), NDUFAF6 (612392), and NDUFAF5 (612360). Mutation in the MTFMT gene (611766), which is involved in mitochondrial translation, has also been reported with complex I deficiency. A mutation has been found in a complex III gene: BCS1L (603647), which is involved in the assembly of complex III. Mutations in complex IV genes include mitochondrial-encoded MTCO3 (516050) and nuclear-encoded COX10 (602125), COX15 (603646), SCO2 (604272), SURF1 (185620), which is involved in the assembly of complex IV, TACO1 (612958), and PET100 (614770). A mutation has been found in a complex V gene: the mitochondrial-encoded MTATP6 (516060). Mutations in genes encoding mitochondrial tRNA proteins have also been identified in patients with Leigh syndrome: see MTTV (590105), MTTK (590060), MTTW (590095), and MTTL1 (590050). Leigh syndrome may also be caused by mutations in components of the pyruvate dehydrogenase complex (e.g., DLD, 238331 and PDHA1, 300502). The French Canadian (or Saguenay-Lac-Saint-Jean) type of Leigh syndrome with COX deficiency (LSFC; 220111) is caused by mutation in the LRPPRC gene (607544). Deficiency of coenzyme Q10 (607426) can present as Leigh syndrome.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 07, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 9:133354702

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 07, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 9:133354702

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 07, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 9:133354702

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

AG

Gene: ACADM
Variant: c.-142C>G
rsID: rs61124994
Ref Allele: C
Alt Allele: G
Freq: 4.4629%uncommon
CADD: 5.026

ClinVar Submissions (1)

- Medium-chain acyl-coenzyme A dehydrogenase deficiency, Autosomal recessive

  ### Medium-chain acyl-coenzyme A dehydrogenase deficiency

  Medium-chain acyl-coenzyme A dehydrogenase (MCAD) is one of the enzymes involved in mitochondrial fatty acid ß-oxidation, which fuels hepatic ketogenesis, a major source of energy once hepatic glycogen stores become depleted during prolonged fasting and periods of higher energy demands. In a typical clinical scenario, a previously healthy child with MCAD deficiency presents with hypoketotic hypoglycemia, vomiting, and lethargy triggered by a common illness. Seizures may occur. Hepatomegaly and liver disease are often present during an acute episode, which can quickly progress to coma and death. Children are normal at birth and – if not identified through newborn screening – typically present between ages three and 24 months; later presentation, even into adulthood, is possible. The prognosis is excellent once the diagnosis is established and frequent feedings are instituted to avoid any prolonged period of fasting.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:75724646

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CG

Gene: ARHGAP31
Variant: c.*2743C>A
rsID: rs78013508
Ref Allele: C
Alt Allele: A
Freq: 4.4757%uncommon
CADD: 0.843

ClinVar Submissions (1)

- Adams-Oliver syndrome

  ### Adams-Oliver syndrome

  Adams-Oliver syndrome (AOS) is characterized by aplasia cutis congenita (ACC) of the scalp and terminal transverse limb defects (TTLD). ACC lesions usually occur in the midline of the parietal or occipital regions, but can also occur on the abdomen or limbs. At birth, an ACC lesion may already have the appearance of a healed scar. ACC lesions less than 5 cm often involve only the skin and almost always heal over a period of months; larger lesions are more likely to involve the skull and possibly the dura, and are at greater risk for complications, which can include infection, hemorrhage, or thrombosis, and can result in death. The limb defects range from mild (unilateral or bilateral short distal phalanges) to severe (complete absence of all toes or fingers, feet or hands, or more, often resembling an amputation). The lower extremities are almost always more severely affected than the upper extremities. Additional major features frequently include cardiovascular malformations/dysfunction (23%), brain anomalies, and less frequently renal, liver, and eye anomalies.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 3:119419007

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

CA

Gene: CRYBB3
Variant: c.314G>A
(p.Arg105Gln)
rsID: rs17670506
Ref Allele: G
Alt Allele: A
Freq: 4.4844%uncommon
CADD: 26.8

ClinVar Submissions (3)

- Cataract, congenital nuclear, autosomal recessive 2, Autosomal dominant

  ### Cataract, congenital nuclear, autosomal recessive 2

  Mutations in the CRYBB3 gene have been identified in families with cataract, described as congenital nuclear cataract with cortical riders, nuclear, posterior polar, anterior polar, and cortical. The preferred title/symbol of this entry was formerly 'Cataract, Congenital Nuclear, Autosomal Recessive 2; CATCN2.'

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 26, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 22:25203882

- Congenital nuclear cataract

  ### Congenital nuclear cataract

  A type of congenital cataract in which the opacities are confined to a small central area within the embryonic or fetal nuclei of the Iens. The remaining lens is clear. [HPO:probinson]

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 26, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 22:25203882

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 26, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 22:25203882

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: PLOD1
Variant: c.644-17T>G
rsID: rs41307745
Ref Allele: T
Alt Allele: G
Freq: 4.5195%uncommon
CADD: 13.82

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 07, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 1:11956900

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Homo

GG

Gene: GAA
Variant: c.1888+21G>A
rsID: rs2304837
Ref Allele: G
Alt Allele: A
Freq: 4.5378%uncommon
CADD: 4.656

ClinVar Submissions (3)

- Glycogen storage disease, type II, Autosomal recessive

  ### Glycogen storage disease, type II

  Pompe disease is classified by age of onset, organ involvement, severity, and rate of progression. Infantile-onset Pompe disease (IOPD; individuals with onset before age 12 months with cardiomyopathy) may be apparent in utero but more typically onset is at the median age of four months with hypotonia, generalized muscle weakness, feeding difficulties, failure to thrive, respiratory distress, and hypertrophic cardiomyopathy. Without treatment by enzyme replacement therapy (ERT), IOPD commonly results in death by age two years from progressive left ventricular outflow obstruction and respiratory insufficiency. Late-onset Pompe disease (LOPD; including: (a) individuals with onset before age 12 months without cardiomyopathy; and (b) all individuals with onset after age 12 months) is characterized by proximal muscle weakness and respiratory insufficiency; clinically significant cardiac involvement is uncommon.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 08, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 17:80112732

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 08, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 17:80112732

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Dec 08, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 17:80112732

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: GAA
Variant: c.2065G>A
(p.Glu689Lys)
rsID: rs1800309
Ref Allele: G
Alt Allele: A
Freq: 4.5426%uncommon
CADD: 18.3

ClinVar Submissions (8)

- Acid alpha-glucosidase, allele 4

  ### Acid alpha-glucosidase, allele 4

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 09, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 8
  Clinical Significance: Conflicting interpretations of pathogenicity, other
  Assembly: GRCh38
  Chromosome/Position: 17:80113242
  OMIM Allelic Variant: 606800.0011

- Glycogen storage disease, type II

  ### Glycogen storage disease, type II

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 09, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 8
  Clinical Significance: Conflicting interpretations of pathogenicity, other
  Assembly: GRCh38
  Chromosome/Position: 17:80113242
  OMIM Allelic Variant: 606800.0011

- not provided

  ### not provided

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 09, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 8
  Clinical Significance: Conflicting interpretations of pathogenicity, other
  Assembly: GRCh38
  Chromosome/Position: 17:80113242
  OMIM Allelic Variant: 606800.0011

- not specified

  ### not specified

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jul 09, 2018
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 8
  Clinical Significance: Conflicting interpretations of pathogenicity, other
  Assembly: GRCh38
  Chromosome/Position: 17:80113242
  OMIM Allelic Variant: 606800.0011

Low clinical importance, Uncertain benign — This is also known as the GAA*4 allozyme is frequent in the Asian population and appears to have somewhat reduced enzyme activity. Kroos et al. rule out pathogenic effect.

Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (5)

Hetero

GA

Gene: TCF12
Variant: c.297A>G
(p.Pro99=)
rsID: rs34560099
Ref Allele: A
Alt Allele: G
Freq: 4.6158%uncommon
CADD: 18.72

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Feb 12, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 15:57091863

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

AG

Gene: GNPTAB
Variant: c.*1457A>G
rsID: rs10219650
Ref Allele: T
Alt Allele: C
Freq: 4.6174%uncommon
CADD: 7.831

ClinVar Submissions (1)

- Mucolipidosis, Type II

  ### Mucolipidosis, Type II

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 12:101745707

- Mucolipidosis, Type III Alpha/Beta

  ### Mucolipidosis, Type III Alpha/Beta

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 12:101745707

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

TC

Gene: ANO10
Variant: c.1682C>T
(p.Thr561Met)
rsID: rs17409162
Ref Allele: G
Alt Allele: A
Freq: 4.6357%uncommon
CADD: 25.2

ClinVar Submissions (4)

- Autosomal recessive cerebellar ataxia

  ### Autosomal recessive cerebellar ataxia

  Autosomal recessive cerebellar ataxias (ARCA) are a heterogeneous group of rare neurological disorders involving both the central and peripheral nervous system (and in some cases other systems and organs), and characterized by degeneration or abnormal development of the cerebellum and spinal cord and, in most cases, early onset occurring before the age of 20 years.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 3:43549835

- Spinocerebellar ataxia, autosomal recessive 10, Autosomal recessive

  ### Spinocerebellar ataxia, autosomal recessive 10

  Autosomal recessive spinocerebellar ataxia-10 is an autosomal recessive neurodegenerative disorder with onset in the teenage or young adult years of gait and limb ataxia, dysarthria, and nystagmus associated with marked cerebellar atrophy on brain imaging (summary by Vermeer et al., 2010). Some patients have low levels of coenzyme Q10 (CoQ10) in muscle and may show some clinical improvement with CoQ10 treatment (Balreira et al., 2014).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 3:43549835

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 3:43549835

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed

Hetero

GA

Gene: PNPLA3
Variant: c.*1090A>G
rsID: rs9626058
Ref Allele: A
Alt Allele: G
Freq: 4.6421%uncommon
CADD: 1.498

ClinVar Submissions (1)

- Susceptibility to Nonalcoholic Fatty Liver Disease

  ### Susceptibility to Nonalcoholic Fatty Liver Disease

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 22:43947472

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

AG

Gene: ECE1
Variant: c.1022C>T
(p.Thr341Ile)
rsID: rs1076669
Ref Allele: G
Alt Allele: A
Freq: 4.6875%uncommon
CADD: 18.27

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 1:21247362

Benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OpenSNP
- PubMed (2)

Hetero

GA

Gene: DGAT1
Variant: c.579C>T
(p.Gly193=)
rsID: rs56180335
Ref Allele: G
Alt Allele: A
Freq: 4.6899%uncommon
CADD: 9.279

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Mar 29, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 8:144318358

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: C8orf37
Variant: c.*2163T>C
rsID: rs75940981
Ref Allele: A
Alt Allele: G
Freq: 4.6915%uncommon
CADD: 2.927

ClinVar Submissions (1)

- Cone-Rod Dystrophy, Recessive

  ### Cone-Rod Dystrophy, Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 8:95245454

- Retinitis Pigmentosa, Recessive

  ### Retinitis Pigmentosa, Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 8:95245454

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

AG

Gene: MC1R
Variant: c.451C>T
(p.Arg151Cys)
rsID: rs1805007
Ref Allele: C
Alt Allele: T
Freq: 4.701%uncommon
CADD: 25.5

ClinVar Submissions (5)

- Cutaneous malignant melanoma 5

  ### Cutaneous malignant melanoma 5

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 5
  Clinical Significance: Conflicting interpretations of pathogenicity, Affects, association, risk factor
  Assembly: GRCh38
  Chromosome/Position: 16:89919709
  OMIM Allelic Variant: 155555.0004

- Increased analgesia from kappa-opioid receptor agonist, female-specific

  ### Increased analgesia from kappa-opioid receptor agonist, female-specific

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 5
  Clinical Significance: Conflicting interpretations of pathogenicity, Affects, association, risk factor
  Assembly: GRCh38
  Chromosome/Position: 16:89919709
  OMIM Allelic Variant: 155555.0004

- Malignant Melanoma Susceptibility

  ### Malignant Melanoma Susceptibility

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 5
  Clinical Significance: Conflicting interpretations of pathogenicity, Affects, association, risk factor
  Assembly: GRCh38
  Chromosome/Position: 16:89919709
  OMIM Allelic Variant: 155555.0004

- OCULOCUTANEOUS ALBINISM, TYPE II, MODIFIER OF

  ### OCULOCUTANEOUS ALBINISM, TYPE II, MODIFIER OF

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 5
  Clinical Significance: Conflicting interpretations of pathogenicity, Affects, association, risk factor
  Assembly: GRCh38
  Chromosome/Position: 16:89919709
  OMIM Allelic Variant: 155555.0004

- Skin/hair/eye pigmentation 2, red hair/fair skin

  ### Skin/hair/eye pigmentation 2, red hair/fair skin

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 5
  Clinical Significance: Conflicting interpretations of pathogenicity, Affects, association, risk factor
  Assembly: GRCh38
  Chromosome/Position: 16:89919709
  OMIM Allelic Variant: 155555.0004

- not provided

  ### not provided

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 5
  Clinical Significance: Conflicting interpretations of pathogenicity, Affects, association, risk factor
  Assembly: GRCh38
  Chromosome/Position: 16:89919709
  OMIM Allelic Variant: 155555.0004

- not specified

  ### not specified

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 04, 2017
  Review Status: criteria provided, conflicting interpretations
  Number of Submitters: 5
  Clinical Significance: Conflicting interpretations of pathogenicity, Affects, association, risk factor
  Assembly: GRCh38
  Chromosome/Position: 16:89919709
  OMIM Allelic Variant: 155555.0004

Insufficiently evaluated benign — The MC1R gene encodes for a receptor protein for a melanin-stimulating hormone, so it is involved in melanogenesis (melanin production). Polymorphisms of this gene have been shown to cause increased susceptibility of skin cells to UV damage. Arg151Cys has been associated with melanoma.

Clinically Significant Conflicting/Uncertain

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (49)

Hetero

CT

Gene: GAN
Variant: c.*294A>G
rsID: rs16955210
Ref Allele: A
Alt Allele: G
Freq: 4.7106%uncommon
CADD: 7.441

ClinVar Submissions (1)

- Giant axonal neuropathy, Autosomal recessive

  ### Giant axonal neuropathy

  Giant axonal neuropathy (GAN) is an early-onset fatal neurodegenerative disorder. GAN starts as severe peripheral motor and sensory neuropathy during infancy and evolves into central nervous system impairment (intellectual disability, seizures, cerebellar signs, and pyramidal tract signs). Most individuals become wheelchair dependent in the second decade of life and eventually bedridden with severe polyneuropathy, ataxia, and dementia. Death usually occurs in the third decade.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 16:81377890

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

AG

Gene: RYR1
Variant: c.11907+22G>A
rsID: rs45555835
Ref Allele: G
Alt Allele: A
Freq: 4.7178%uncommon
CADD: 2.072

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Oct 29, 2013
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 19:38543682

Benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: NSD1
Variant: c.6782T>C
(p.Met2261Thr)
rsID: rs34165241
Ref Allele: T
Alt Allele: C
Freq: 4.7233%uncommon
CADD: 0.031

ClinVar Submissions (6)

- Beckwith-Wiedemann syndrome, Autosomal dominant

  ### Beckwith-Wiedemann syndrome

  Beckwith-Wiedemann syndrome (BWS) is a growth disorder variably characterized by neonatal hypoglycemia, macrosomia, macroglossia, hemihyperplasia, omphalocele, embryonal tumors (e.g., Wilms tumor, hepatoblastoma, neuroblastoma, and rhabdomyosarcoma), visceromegaly, adrenocortical cytomegaly, renal abnormalities (e.g., medullary dysplasia, nephrocalcinosis, medullary sponge kidney, and nephromegaly), and ear creases/pits. BWS is considered a clinical spectrum, in which affected individuals may have many of these features or may have only one or two clinical features. Early death may occur from complications of prematurity, hypoglycemia, cardiomyopathy, macroglossia, or tumors. However, the previously reported mortality of 20% is likely an overestimate given better recognition of the disorder along with enhanced treatment options. Macroglossia and macrosomia are generally present at birth but may have postnatal onset. Growth rate slows around age seven to eight years. Hemihyperplasia may affect segmental regions of the body or selected organs and tissues.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 01, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 5:177294150

- History of neurodevelopmental disorder

  ### History of neurodevelopmental disorder

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 01, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 5:177294150

- Sotos syndrome

  ### Sotos syndrome

  Sotos syndrome is a disorder characterized by a distinctive facial appearance, overgrowth in childhood, and learning disabilities or delayed development of mental and movement abilities. Characteristic facial features include a long, narrow face; a high forehead; flushed (reddened) cheeks; and a small, pointed chin. In addition, the outside corners of the eyes may point downward (down-slanting palpebral fissures). This facial appearance is most notable in early childhood. Affected infants and children tend to grow quickly; they are significantly taller than their siblings and peers and have an unusually large head. However, adult height is usually in the normal range.People with Sotos syndrome often have intellectual disability, and most also have behavioral problems. Frequent behavioral issues include attention deficit hyperactivity disorder (ADHD), phobias, obsessions and compulsions, tantrums, and impulsive behaviors. Problems with speech and language are also common. Affected individuals often have a stutter, a monotone voice, and problems with sound production. Additionally, weak muscle tone (hypotonia) may delay other aspects of early development, particularly motor skills such as sitting and crawling.Other signs and symptoms of Sotos syndrome can include an abnormal side-to-side curvature of the spine (scoliosis), seizures, heart or kidney defects, hearing loss, and problems with vision. Some infants with this disorder experience yellowing of the skin and whites of the eyes (jaundice) and poor feeding.A small percentage of people with Sotos syndrome have developed cancer, most often in childhood, but no single form of cancer occurs most frequently with this condition. It remains uncertain whether Sotos syndrome increases the risk of specific types of cancer. If people with this disorder have an increased cancer risk, it is only slightly greater than that of the general population.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 01, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 5:177294150

- Weaver syndrome, Autosomal dominant

  ### Weaver syndrome

  EZH2-related overgrowth includes EZH2-related Weaver syndrome at one end of the spectrum and tall stature at the other. Although most individuals diagnosed with a heterozygous EZH2 pathogenic variant have been identified because of a clinical suspicion of Weaver syndrome, a minority have been identified through molecular genetic testing of family members of probands or individuals with overgrowth who did not have a clinical diagnosis of Weaver syndrome. Thus, the extent of the phenotypic spectrum associated with a heterozygous EZH2 pathogenic variant is not yet known. Weaver syndrome is characterized by tall stature, variable intellect (ranging from normal intellect to severe intellectual disability), characteristic facial appearance, and a range of associated clinical features including advanced bone age, poor coordination, soft doughy skin, camptodactyly of the fingers and/or toes, umbilical hernia, abnormal tone, and hoarse low cry in infancy. Brain MRI has identified abnormalities in a few individuals with EZH2-related overgrowth. Neuroblastoma occurs at a slightly increased frequency in individuals with a heterozygous EZH2 pathogenic variant but data are insufficient to determine absolute risk. There is currently no evidence that additional malignancies (including hematologic malignancies) occur with increased frequency.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 01, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 5:177294150

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 01, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 5:177294150

Benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (4)

Hetero

TC

Gene: NSD1
Variant: c.5623-22G>A
rsID: rs79098301
Ref Allele: G
Alt Allele: A
Freq: 4.7257%uncommon
CADD: 0.005

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:177280543

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (1)

Hetero

GA

Gene: NSD1
Variant: c.6750G>A
(p.Met2250Ile)
rsID: rs35848863
Ref Allele: G
Alt Allele: A
Freq: 4.7257%uncommon
CADD: 11.72

ClinVar Submissions (6)

- Beckwith-Wiedemann syndrome, Autosomal dominant

  ### Beckwith-Wiedemann syndrome

  Beckwith-Wiedemann syndrome (BWS) is a growth disorder variably characterized by neonatal hypoglycemia, macrosomia, macroglossia, hemihyperplasia, omphalocele, embryonal tumors (e.g., Wilms tumor, hepatoblastoma, neuroblastoma, and rhabdomyosarcoma), visceromegaly, adrenocortical cytomegaly, renal abnormalities (e.g., medullary dysplasia, nephrocalcinosis, medullary sponge kidney, and nephromegaly), and ear creases/pits. BWS is considered a clinical spectrum, in which affected individuals may have many of these features or may have only one or two clinical features. Early death may occur from complications of prematurity, hypoglycemia, cardiomyopathy, macroglossia, or tumors. However, the previously reported mortality of 20% is likely an overestimate given better recognition of the disorder along with enhanced treatment options. Macroglossia and macrosomia are generally present at birth but may have postnatal onset. Growth rate slows around age seven to eight years. Hemihyperplasia may affect segmental regions of the body or selected organs and tissues.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 01, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 5:177294118

- History of neurodevelopmental disorder

  ### History of neurodevelopmental disorder

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 01, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 5:177294118

- Sotos syndrome

  ### Sotos syndrome

  Sotos syndrome is a disorder characterized by a distinctive facial appearance, overgrowth in childhood, and learning disabilities or delayed development of mental and movement abilities. Characteristic facial features include a long, narrow face; a high forehead; flushed (reddened) cheeks; and a small, pointed chin. In addition, the outside corners of the eyes may point downward (down-slanting palpebral fissures). This facial appearance is most notable in early childhood. Affected infants and children tend to grow quickly; they are significantly taller than their siblings and peers and have an unusually large head. However, adult height is usually in the normal range.People with Sotos syndrome often have intellectual disability, and most also have behavioral problems. Frequent behavioral issues include attention deficit hyperactivity disorder (ADHD), phobias, obsessions and compulsions, tantrums, and impulsive behaviors. Problems with speech and language are also common. Affected individuals often have a stutter, a monotone voice, and problems with sound production. Additionally, weak muscle tone (hypotonia) may delay other aspects of early development, particularly motor skills such as sitting and crawling.Other signs and symptoms of Sotos syndrome can include an abnormal side-to-side curvature of the spine (scoliosis), seizures, heart or kidney defects, hearing loss, and problems with vision. Some infants with this disorder experience yellowing of the skin and whites of the eyes (jaundice) and poor feeding.A small percentage of people with Sotos syndrome have developed cancer, most often in childhood, but no single form of cancer occurs most frequently with this condition. It remains uncertain whether Sotos syndrome increases the risk of specific types of cancer. If people with this disorder have an increased cancer risk, it is only slightly greater than that of the general population.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 01, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 5:177294118

- Weaver syndrome, Autosomal dominant

  ### Weaver syndrome

  EZH2-related overgrowth includes EZH2-related Weaver syndrome at one end of the spectrum and tall stature at the other. Although most individuals diagnosed with a heterozygous EZH2 pathogenic variant have been identified because of a clinical suspicion of Weaver syndrome, a minority have been identified through molecular genetic testing of family members of probands or individuals with overgrowth who did not have a clinical diagnosis of Weaver syndrome. Thus, the extent of the phenotypic spectrum associated with a heterozygous EZH2 pathogenic variant is not yet known. Weaver syndrome is characterized by tall stature, variable intellect (ranging from normal intellect to severe intellectual disability), characteristic facial appearance, and a range of associated clinical features including advanced bone age, poor coordination, soft doughy skin, camptodactyly of the fingers and/or toes, umbilical hernia, abnormal tone, and hoarse low cry in infancy. Brain MRI has identified abnormalities in a few individuals with EZH2-related overgrowth. Neuroblastoma occurs at a slightly increased frequency in individuals with a heterozygous EZH2 pathogenic variant but data are insufficient to determine absolute risk. There is currently no evidence that additional malignancies (including hematologic malignancies) occur with increased frequency.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 01, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 5:177294118

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 01, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 6
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 5:177294118

Benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (4)

Hetero

GA

Gene: MC4R
Variant: c.-178A>C
rsID: rs34114122
Ref Allele: T
Alt Allele: G
Freq: 4.7273%uncommon
CADD: 6.786

ClinVar Submissions (1)

- Obesity, Autosomal dominant

  ### Obesity

  A status with BODY WEIGHT that is grossly above the acceptable or desirable weight, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 18:60372527

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

TG

Gene: NSD1
Variant: c.*3338A>C
rsID: rs75587357
Ref Allele: A
Alt Allele: C
Freq: 4.7361%uncommon
CADD: 4.378

ClinVar Submissions (1)

- Sotos syndrome

  ### Sotos syndrome

  Sotos syndrome is a disorder characterized by a distinctive facial appearance, overgrowth in childhood, and learning disabilities or delayed development of mental and movement abilities. Characteristic facial features include a long, narrow face; a high forehead; flushed (reddened) cheeks; and a small, pointed chin. In addition, the outside corners of the eyes may point downward (down-slanting palpebral fissures). This facial appearance is most notable in early childhood. Affected infants and children tend to grow quickly; they are significantly taller than their siblings and peers and have an unusually large head. However, adult height is usually in the normal range.People with Sotos syndrome often have intellectual disability, and most also have behavioral problems. Frequent behavioral issues include attention deficit hyperactivity disorder (ADHD), phobias, obsessions and compulsions, tantrums, and impulsive behaviors. Problems with speech and language are also common. Affected individuals often have a stutter, a monotone voice, and problems with sound production. Additionally, weak muscle tone (hypotonia) may delay other aspects of early development, particularly motor skills such as sitting and crawling.Other signs and symptoms of Sotos syndrome can include an abnormal side-to-side curvature of the spine (scoliosis), seizures, heart or kidney defects, hearing loss, and problems with vision. Some infants with this disorder experience yellowing of the skin and whites of the eyes (jaundice) and poor feeding.A small percentage of people with Sotos syndrome have developed cancer, most often in childhood, but no single form of cancer occurs most frequently with this condition. It remains uncertain whether Sotos syndrome increases the risk of specific types of cancer. If people with this disorder have an increased cancer risk, it is only slightly greater than that of the general population.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 5:177298797

- Weaver syndrome, Autosomal dominant

  ### Weaver syndrome

  EZH2-related overgrowth includes EZH2-related Weaver syndrome at one end of the spectrum and tall stature at the other. Although most individuals diagnosed with a heterozygous EZH2 pathogenic variant have been identified because of a clinical suspicion of Weaver syndrome, a minority have been identified through molecular genetic testing of family members of probands or individuals with overgrowth who did not have a clinical diagnosis of Weaver syndrome. Thus, the extent of the phenotypic spectrum associated with a heterozygous EZH2 pathogenic variant is not yet known. Weaver syndrome is characterized by tall stature, variable intellect (ranging from normal intellect to severe intellectual disability), characteristic facial appearance, and a range of associated clinical features including advanced bone age, poor coordination, soft doughy skin, camptodactyly of the fingers and/or toes, umbilical hernia, abnormal tone, and hoarse low cry in infancy. Brain MRI has identified abnormalities in a few individuals with EZH2-related overgrowth. Neuroblastoma occurs at a slightly increased frequency in individuals with a heterozygous EZH2 pathogenic variant but data are insufficient to determine absolute risk. There is currently no evidence that additional malignancies (including hematologic malignancies) occur with increased frequency.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 5:177298797

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

AC

Gene: DIS3L2
Variant: c.*103A>G
rsID: rs113002914
Ref Allele: A
Alt Allele: G
Freq: 4.7504%uncommon
CADD: 14.17

ClinVar Submissions (1)

- Renal hamartomas nephroblastomatosis and fetal gigantism, Autosomal recessive

  ### Renal hamartomas nephroblastomatosis and fetal gigantism

  Perlman syndrome is an autosomal recessive congenital overgrowth syndrome with similarities to Beckwith-Wiedemann syndrome (BWS; 130650). Affected children are large at birth, are hypotonic, and show organomegaly, characteristic facial dysmorphisms (inverted V-shaped upper lip, prominent forehead, deep-set eyes, broad and flat nasal bridge, and low-set ears), renal anomalies (nephromegaly and hydronephrosis), frequent neurodevelopmental delay, and high neonatal mortality. Perlman syndrome is associated with a high risk of Wilms tumor, with a 64% incidence in infants surviving beyond the neonatal period. The tumor is diagnosed at an earlier age in these individuals compared with sporadic cases (less than 2 years and 3-4 years of age, respectively), and there is a high frequency of bilateral tumors (55%). Histologic examination of the kidneys in children with Perlman syndrome shows frequent nephroblastomatosis, which is a precursor lesion for Wilms tumor (summary by Astuti et al., 2012).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:232336733

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

AG

Gene: SLC35C1
Variant: c.*414G>A
rsID: rs1139267
Ref Allele: G
Alt Allele: A
Freq: 4.7504%uncommon
CADD: 6.406

ClinVar Submissions (1)

- Congenital disorder of glycosylation

  ### Congenital disorder of glycosylation

  A genetically heterogeneous group of heritable disorders resulting from defects in protein N-glycosylation.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:45811749

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: ABCC8;KCNJ11
Variant: c.4714G>A
(p.Val1572Ile)
rsID: rs8192690
Ref Allele: C
Alt Allele: T
Freq: 4.7703%uncommon
CADD: 12.22

ClinVar Submissions (3)

- Hyperinsulinism, Dominant/Recessive

  ### Hyperinsulinism, Dominant/Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:17393023

- Maturity onset diabetes mellitus in young, Autosomal dominant

  ### Maturity onset diabetes mellitus in young

  Maturity-onset diabetes of the young is an autosomal dominant form of diabetes typically occurring before 25 years of age and caused by primary insulin secretion defects. Despite its low prevalence, MODY is not a single entity but represents genetic, metabolic, and clinical heterogeneity (Vaxillaire and Froguel, 2008). Genetic Heterogeneity of MODY MODY1 (125850) is caused by heterozygous mutation in the hepatocyte nuclear factor-4-alpha gene (HNF4A; 600281) on chromosome 20. MODY2 (125851) is caused by heterozygous mutation in the glucokinase gene (GCK; 138079) on chromosome 7. MODY3 (600496) is caused by heterozygous mutation in the hepatocyte nuclear factor-1alpha gene (HNF1A; 142410) on chromosome 12q24.2. MODY4 (606392) is caused by heterozygous mutation in the pancreas/duodenum homeobox protein-1 gene (PDX1; 600733) on chromosome 13q12.1. MODY5 (137920) is caused by heterozygous mutation in the gene encoding hepatic transcription factor-2 (TCF2; 189907) on chromosome 17cen-q21.3. MODY6 (606394) is caused by heterozygous mutation in the NEUROD1 gene (601724) on chromosome 2q32. MODY7 (610508) is caused by heterozygous mutation in the KLF11 gene (603301) on chromosome 2p25. MODY8 (609812), or diabetes-pancreatic exocrine dysfunction syndrome, is caused by heterozygous mutation in the CEL gene (114840) on chromosome 9q34. MODY9 (612225) is caused by heterozygous mutation in the PAX4 gene (167413) on chromosome 7q32. MODY10 (613370) is caused by heterozygous mutation in the insulin gene (INS; 176730) on chromosome 11p15.5. MODY11 (613375) is caused by heterozygous mutation in the BLK gene (191305) on chromosome 8p23. MODY13 (616329) is caused by heterozygous mutation in the KCNJ11 gene (600937) on chromosome 11p15. MODY14 (616511) is caused by heterozygous mutation in the APPL1 gene (604299) on chromosome 3p14.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:17393023

- Permanent neonatal diabetes mellitus, Autosomal dominant

  ### Permanent neonatal diabetes mellitus

  Permanent neonatal diabetes mellitus (PNDM) is characterized by the onset of hyperglycemia within the first six months of life (mean age: 7 weeks; range: birth to 26 weeks). The diabetes mellitus is associated with partial or complete insulin deficiency. Clinical manifestations at the time of diagnosis include intrauterine growth retardation, hyperglycemia, glycosuria, osmotic polyuria, severe dehydration, and failure to thrive. Therapy with insulin corrects the hyperglycemia and results in dramatic catch-up growth. The course of PNDM varies by genotype.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:17393023

- Transient Neonatal Diabetes, Dominant

  ### Transient Neonatal Diabetes, Dominant

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:17393023

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 3
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 11:17393023

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (1)

Hetero

CT

Gene: PNPLA3
Variant: c.*429T>C
rsID: rs41278873
Ref Allele: T
Alt Allele: C
Freq: 4.7711%uncommon
CADD: 0.011

ClinVar Submissions (1)

- Susceptibility to Nonalcoholic Fatty Liver Disease

  ### Susceptibility to Nonalcoholic Fatty Liver Disease

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 22:43946811

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

TC

Gene: MAP3K1
Variant: c.1566C>T
(p.Thr522=)
rsID: rs2229882
Ref Allele: C
Alt Allele: T
Freq: 4.7855%uncommon
CADD: 0.148

ClinVar Submissions (1)

- 46,XY sex reversal, type 6, Autosomal dominant

  ### 46,XY sex reversal, type 6

  Nonsyndromic disorders of testicular development are a group of conditions characterized by the following: A generally normal physical examination with absence of clinical findings involving organ systems other than the reproductive organs. A normal 46,XY karyotype by conventional staining. External genitalia that range from ambiguous to normal female. Internal genitalia that range from absent müllerian structures to a fully developed uterus and fallopian tubes. Gonads that are characterized as normal testis, ovotestis, dysgenetic testis, or streak. Based on the particular features seen in any given individual, the clinical diagnosis may be designated as 46,XY disorder of sex development (DSD) or 46,XY complete gonadal dysgenesis (CDG).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 26, 2017
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 5:56872885

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (2)

Hetero

CT

Gene: GHSR
Variant: c.*792G>C
rsID: rs9880652
Ref Allele: C
Alt Allele: G
Freq: 4.8022%uncommon
CADD: 0.021

ClinVar Submissions (1)

- Short stature, idiopathic, autosomal, Autosomal dominant

  ### Short stature, idiopathic, autosomal

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 3:172444369

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CG

Gene: SF3B4
Variant: c.-234T>C
rsID: rs72692813
Ref Allele: A
Alt Allele: G
Freq: 4.8237%uncommon
CADD: 7.859

ClinVar Submissions (1)

- Nager syndrome, Autosomal dominant

  ### Nager syndrome

  Nager syndrome is the prototype for a group of disorders collectively referred to as the acrofacial dysostoses (AFDs), which are characterized by malformation of the craniofacial skeleton and the limbs. The major facial features of Nager syndrome include downslanted palpebral fissures, midface retrusion, and micrognathia, the latter of which often requires the placement of a tracheostomy in early childhood. Limb defects typically involve the anterior (radial) elements of the upper limbs and manifest as small or absent thumbs, triphalangeal thumbs, radial hypoplasia or aplasia, and radioulnar synostosis. Phocomelia of the upper limbs and, occasionally, lower-limb defects have also been reported. The presence of anterior upper-limb defects and the typical lack of lower-limb involvement distinguishes Nager syndrome from Miller syndrome (263750), another rare AFD; however, distinguishing Nager syndrome from other AFDs, including Miller syndrome, can be challenging (summary by Bernier et al., 2012).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 1:149927993

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

AG

Gene: DDOST;PINK1;PINK1-AS
Variant: c.*457A>C
rsID: rs150466875
Ref Allele: T
Alt Allele: G
Freq: 4.8285%uncommon
CADD: 5.179

ClinVar Submissions (1)

- Congenital disorder of glycosylation

  ### Congenital disorder of glycosylation

  A genetically heterogeneous group of heritable disorders resulting from defects in protein N-glycosylation.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:20651922

- Parkinson Disease, Recessive

  ### Parkinson Disease, Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 1:20651922

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

TG

Gene: WDR62
Variant: c.180G>A
(p.Val60=)
rsID: rs61742664
Ref Allele: G
Alt Allele: A
Freq: 4.8332%uncommon
CADD: 19.64

ClinVar Submissions (5)

- Primary Microcephaly 2 With or Without Cortical Malformations

  ### Primary Microcephaly 2 With or Without Cortical Malformations

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 05, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 19:36058782

- Primary autosomal recessive microcephaly 2, Autosomal recessive

  ### Primary autosomal recessive microcephaly 2

  Microcephaly-2 with or without cortical malformations is an autosomal recessive neurodevelopmental disorder showing phenotypic variability. Classically, primary microcephaly is a clinical diagnosis made when an individual has a head circumference more than 3 standard deviations (SD) below the age- and sex-matched population mean, and mental retardation with no other associated malformations and with no apparent etiology (Hofman, 1984). Patients with WDR62 mutations have head circumferences ranging from low-normal to severe (-9.8 SD), and most patients with brain scans have shown various types of cortical malformations. All have delayed psychomotor development; seizures are variable (summary by Yu et al., 2010). For a general phenotypic description and a discussion of genetic heterogeneity of primary microcephaly, see MCPH1 (251200).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 05, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 19:36058782

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 05, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 5
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 19:36058782

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (2)

Hetero

GA

Gene: RUNX1
Variant: c.*2474T>C
rsID: rs56202419
Ref Allele: A
Alt Allele: G
Freq: 4.8516%uncommon
CADD: 0.332

ClinVar Submissions (1)

- Familial platelet disorder with associated myeloid malignancy, Autosomal dominant

  ### Familial platelet disorder with associated myeloid malignancy

  Disease that is characterised by moderate thrombocytopenia, abnormal platelet function and the propensity to develop myeloid malignancies, in particular acute myelogenous leukaemia. The prevalence is unknown but the disease has been reported in less than 20 families. Causative mutations have been identified in the RUNX1 gene (also known as AML1 or CBFA2; chromosome 21q22.3) in most of the analysed families. The condition is inherited as an autosomal dominant trait.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 21:34789661

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

AG

Gene: WDR62
Variant: c.1768+28G>A
rsID: rs77938609
Ref Allele: G
Alt Allele: A
Freq: 4.8667%uncommon
CADD: 0.086

ClinVar Submissions (1)

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: -
  Review Status: no assertion criteria provided
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 19:36086840

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

GA

Gene: RUNX1
Variant: c.1389C>G
(p.Pro463=)
rsID: rs61750222
Ref Allele: G
Alt Allele: C
Freq: 4.9009%uncommon
CADD: 9.182

ClinVar Submissions (2)

- Familial platelet disorder with associated myeloid malignancy, Autosomal dominant

  ### Familial platelet disorder with associated myeloid malignancy

  Disease that is characterised by moderate thrombocytopenia, abnormal platelet function and the propensity to develop myeloid malignancies, in particular acute myelogenous leukaemia. The prevalence is unknown but the disease has been reported in less than 20 families. Causative mutations have been identified in the RUNX1 gene (also known as AML1 or CBFA2; chromosome 21q22.3) in most of the analysed families. The condition is inherited as an autosomal dominant trait.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 03, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 21:34792189

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Apr 03, 2018
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 2
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 21:34792189

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (1)

Hetero

GC

Gene: C8orf37
Variant: c.*2525T>C
rsID: rs74318654
Ref Allele: A
Alt Allele: G
Freq: 4.9224%uncommon
CADD: 5.752

ClinVar Submissions (1)

- Cone-Rod Dystrophy, Recessive

  ### Cone-Rod Dystrophy, Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 8:95245092

- Retinitis Pigmentosa, Recessive

  ### Retinitis Pigmentosa, Recessive

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 8:95245092

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

AG

Gene: PHOX2B
Variant: c.*1662A>T
rsID: rs1063611
Ref Allele: T
Alt Allele: A
Freq: 4.9368%uncommon
CADD: 23.3

ClinVar Submissions (1)

- Congenital central hypoventilation, Autosomal dominant

  ### Congenital central hypoventilation

  Congenital central hypoventilation syndrome (CCHS) is a rare disorder of respiratory and autonomic regulation. It is typically characterized by a classic presentation in newborns and, rarely, a milder later-onset (LO-CCHS) presentation in toddlers, children, and adults. Classic CCHS presents in newborns as: Apparent hypoventilation with monotonous respiratory rates and shallow breathing either during sleep only or while awake as well as asleep; Autonomic nervous system dysregulation (ANSD); and In some individuals, altered development of neural crest-derived structures (i.e., Hirschsprung disease) and/or tumors of neural crest origin (neuroblastoma, ganglioneuroma, and ganglioneuroblastoma). Individuals with CCHS who have been diagnosed as newborns and ventilated conservatively and consistently throughout childhood have now reached the age of 20 to 30 years; they are highly functional and live independently. LO-CCHS manifests as nocturnal alveolar hypoventilation and mild ANSD. Individuals with LO-CCHS who were not identified until age 20 years or older have now reached the age of 30 to 55 years.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 4:41744145

- Neuroblastoma, Autosomal dominant

  ### Neuroblastoma

  ALK-related neuroblastic tumor susceptibility is characterized by increased risk for neuroblastic tumors including neuroblastoma, ganglioneuroblastoma, and ganglioneuroma. Neuroblastoma is a more malignant tumor and ganglioneuroma a more benign tumor. Depending on the histologic findings, ganglioneuroblastoma can behave in a more aggressive fashion, like neuroblastoma, or in a benign fashion, like ganglioneuroma. Preliminary data from the ten reported families with ALK-related neuroblastic tumor susceptibility suggest an overall penetrance of approximately 57% with the risk for neuroblastic tumor development highest in infancy and decreasing by late childhood.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Benign
  Assembly: GRCh38
  Chromosome/Position: 4:41744145

Benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed (2)

Hetero

TA

Gene: DIAPH1
Variant: c.117+14C>T
rsID: rs2074913
Ref Allele: G
Alt Allele: A
Freq: 4.9535%uncommon
CADD: 18.02

ClinVar Submissions (4)

- Nonsyndromic Hearing Loss, Mixed

  ### Nonsyndromic Hearing Loss, Mixed

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:141618784

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:141618784

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed (2)

Hetero

GA

Gene: MCFD2
Variant: c.*133A>T
rsID: rs75416242
Ref Allele: T
Alt Allele: A
Freq: 4.9877%uncommon
CADD: 10.81

ClinVar Submissions (1)

- Combined deficiency of factor V and factor VIII, 1

  ### Combined deficiency of factor V and factor VIII, 1

  Combined deficiency of factor V (612309) and factor VIII (300841) is characterized by bleeding symptoms similar to those in hemophilia (306700) or parahemophilia (227400), caused by single deficiency of FV or FVIII, respectively. The most common symptoms are epistaxis, menorrhagia, and excessive bleeding during or after trauma. Plasma FV and FVIII antigen and activity levels are in the range of 5 to 30%. Inheritance of F5F8D is autosomal recessive and distinct from the coinheritance of FV deficiency and FVIII deficiency (summary by Zhang and Ginsburg, 2004). Genetic Heterogeneity of Combined Deficiency of Factor V and Factor VIII Another form of combined deficiency of factor V and factor VII (F5F8D2; 613625) is caused by mutation in the MCFD2 gene (607788) on chromosome 2.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 2:46905330

Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

TA

Gene: PKHD1
Variant: c.11509G>A
(p.Val3837Ile)
rsID: rs9474034
Ref Allele: C
Alt Allele: T
Freq: 4.9893%uncommon
CADD: 15.06

ClinVar Submissions (4)

- Autosomal recessive polycystic kidney disease, Autosomal recessive

  ### Autosomal recessive polycystic kidney disease

  Autosomal recessive polycystic kidney disease (ARPKD) belongs to a group of congenital hepatorenal fibrocystic syndromes and is a cause of significant renal and liver-related morbidity and mortality in children. The majority of individuals with ARPKD present in the neonatal period with enlarged echogenic kidneys. Renal disease is characterized by nephromegaly, hypertension, and varying degrees of renal dysfunction. More than 50% of affected individuals with ARPKD progress to end-stage renal disease (ESRD) within the first decade of life; ESRD may require kidney transplantation. Pulmonary hypoplasia resulting from oligohydramnios occurs in a number of affected infants. Approximately 30% of these infants die in the neonatal period or within the first year of life from respiratory insufficiency or superimposed pulmonary infections. With neonatal respiratory support and renal replacement therapies, the long-term survival of these infants has improved to greater than 80%. As advances in renal replacement therapy and kidney transplantation improve long-term survival, it is likely that clinical hepatobiliary disease will become a major feature of the natural history of ARPKD. In addition, a subset of individuals with this disorder are identified with hepatosplenomegaly; the renal disease is often mild and may be discovered incidentally during imaging studies of the abdomen. Approximately 50% of infants will have clinical evidence of liver involvement at diagnosis although histologic hepatic fibrosis is invariably present at birth. This can lead to progressive portal hypertension with resulting esophageal or gastric varices, enlarged hemorrhoids, splenomegaly, hypersplenism, protein-losing enteropathy, and gastrointestinal bleeding. Other hepatic findings include nonobstructed dilatation of the intrahepatic bile ducts (Caroli syndrome) and dilatation of the common bile duct, which may lead to recurrent or persistent bacterial ascending cholangitis due to dilated bile ducts and stagnant bile flow. An increasing number of affected individuals surviving the neonatal period will eventually require portosystemic shunting or liver transplantation for complications of portal hypertension or cholangitis. The classic neonatal presentation of ARPKD notwithstanding, there is significant variability in age and presenting clinical symptoms related to the relative degree of renal and biliary abnormalities.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 10, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 6:51632721

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Aug 10, 2017
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 6:51632721

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- UniProt
- OMIM
- OpenSNP
- PubMed (3)

Hetero

CT

Gene: SDHAF1
Variant: c.333C>G
(p.Arg111=)
rsID: rs76336581
Ref Allele: C
Alt Allele: G
Freq: 4.9949%uncommon
CADD: 7.673

ClinVar Submissions (4)

- Mitochondrial complex II deficiency, Autosomal recessive

  ### Mitochondrial complex II deficiency

  Mitochondrial complex II deficiency is an autosomal recessive disorder with a highly variable phenotype. Some patients have multisystem involvement of the brain, heart, muscle, liver, and kidneys resulting in death in infancy, whereas others have only isolated cardiac or muscle involvement with onset in adulthood and normal cognition. Measurement of complex II activity in muscle is the most reliable means of diagnosis; however, there is no clear correlation between residual complex II activity and severity or clinical outcome. In some cases, treatment with riboflavin may have clinical benefit (summary by Jain-Ghai et al., 2013).

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 19:35995607

- not provided

  ### not provided

  The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 19:35995607

- not specified

  ### not specified

  The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, multiple submitters, no conflicts
  Number of Submitters: 4
  Clinical Significance: Benign/Likely benign
  Assembly: GRCh38
  Chromosome/Position: 19:35995607

Benign/Likely benign

- LitVar
- SNPedia
- dbSNP
- OMIM
- OpenSNP
- PubMed

Hetero

CG

Gene: PDE4D
Variant: c.*1251A>G
rsID: rs17719258
Ref Allele: T
Alt Allele: C
Freq: 4.9957%uncommon
CADD: 3.208

ClinVar Submissions (1)

- Acrodysostosis, Autosomal dominant

  ### Acrodysostosis

  A syndrome of short hands and feet, nasal hypoplasia, mental retardation, and characteristic facies.

  View Clinvar Submission

  ### Variant Details

  Last Evaluated: Jun 14, 2016
  Review Status: criteria provided, single submitter
  Number of Submitters: 1
  Clinical Significance: Likely benign
  Assembly: GRCh38
  Chromosome/Position: 5:58973413

Likely benign

- LitVar
- SNPedia
- dbSNP
- OpenSNP
- PubMed

Hetero

TC