Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Link to SEPIO compliant JSON-LD document

Variant: NM_000257.3(MYH7):c.2717A>G (p.Asp906Gly)

CA012936

14125 (ClinVar)

Gene: MYH7

Condition: hypertrophic cardiomyopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 6a11c78d-e05e-417f-8453-1e66356e09e9

HGVS expressions

NM_000257.3:c.2717A>G

NM_000257.3(MYH7):c.2717A>G (p.Asp906Gly)

NM_000257.4:c.2717A>G

ENST00000355349.3:c.2717A>G

NC_000014.9:g.23424112T>C

CM000676.2:g.23424112T>C

NC_000014.8:g.23893321T>C

CM000676.1:g.23893321T>C

NC_000014.7:g.22963161T>C

NG_007884.1:g.16550A>G

Pathogenic

PS4 PP1_Strong PM2 PM1

Evidence Links 5

Expert Panel

Cardiomyopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Cardiomyopathy VCEP

The c.2717A>G (p.Asp906Gly) variant in MYH7 has been reported in >20 individuals with hypertrophic cardiomyopathy (PS4; PMID:27532257; PMID:12081993; PMID:15528230; PMID:16267253; PMID:24510615; Partners LMM ClinVar SCV000059468.5). This variant segregated with disease in 10 affected individuals (PP1_Strong; PMID:12081993; PMID:15528230). This variant was absent from large population studies (PM2; http://exac.broadinstitute.org). This variant lies in the head region of the protein (aa 181-937) and missense variants in this region are statistically more likely to be disease-associated (PM1; PMID:27532257). In summary, this variant meets criteria to be classified as pathogenic for hypertrophic cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (PMID:29300372): PS4; PP1_ Strong; PM1; PM2

PS4

Variant identified in >20 probands with HCM including ClinVar SCV000059468.5

Variant identified in 1 proband with HCM PubMed:16267253

Variant identified in 1 proband with HCM PubMed:15528230

Variant identified in 5 probands with HCM PubMed:24510615

Variant identified in 1 proband with HCM PubMed:12081993

Variant identified in 7 probands with HCM PubMed:27532257

PP1_Strong

10 segregations

2 segregations PubMed:15528230

10 segregations PubMed:12081993

PM2

Absent from ExAC

PM1

Variants in head region of the protein (aa 181-937) are statistically more likely to be disease-associated

Variants in head region of the protein (aa 181-937) are statistically more likely to be disease-associated PubMed:27532257

Approved on: 2016-12-15

Published on: 2018-11-16

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