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]

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Variant: NM_000257.3(MYH7):c.2681A>G (p.Glu894Gly)

CA012832

42922 (ClinVar)

Gene: MYH7

Condition: hypertrophic cardiomyopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: f89b58e9-fd2b-41c7-9ca3-dd7cedfdd3ee

Approved on: 2016-12-15

Published on: 2018-11-16

HGVS expressions

NM_000257.3:c.2681A>G

NM_000257.3(MYH7):c.2681A>G (p.Glu894Gly)

NC_000014.9:g.23424148T>C

CM000676.2:g.23424148T>C

NC_000014.8:g.23893357T>C

CM000676.1:g.23893357T>C

NC_000014.7:g.22963197T>C

NG_007884.1:g.16514A>G

NM_000257.4:c.2681A>G

ENST00000355349.3:c.2681A>G

Pathogenic

PP1_Moderate PM2 PM1 PS4 PP3

Evidence Links 1

Expert Panel

Cardiomyopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Cardiomyopathy VCEP

The c.2681A>G (p.Glu894Gly) variant in MYH7 has been reported in >20 individuals with hypertrophic cardiomyopathy (PS4: PMID:PMID:27532257; PMID:15358028; PMID:15858117; PMID:21511876; PMID:23396983; PMID:24510615; SHaRe consortium, PMID: 30297972, Partners LMM ClinVar SCV000059463.5; AGCMC Sydney ClinVar SCV000212641.2; Invitae ClinVar SCV000253683.5). This variant segregated with disease in 6 affected individuals (PP1_Moderate: AGCMC Sydney ClinVar SCV000212641.2; Partners LMM ClinVar SCV000059463.5). 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). Computational prediction tools and conservation analysis suggest that this variant may impact the protein (PP3). 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; PM1; PM2; PP1_Moderate; PP3

PP1_Moderate

5 segregations from ClinVar SCV000212641.2 and ClinVar SCV000059463.5

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

PS4

>20 HCM probands including SHaRe, ClinVar SCV000059463.5; ClinVar SCV000212641.2; ClinVar SCV000253683.5)

7 probands with HCM identified PubMed:27532257

PP3

Tools predict damaging

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