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.2722C>G (p.Leu908Val)

CA012953

14097 (ClinVar)

Gene: MYH7

Condition: hypertrophic cardiomyopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: bd7ac89f-9ef0-4c1b-9884-893fd733703d

HGVS expressions

NM_000257.3:c.2722C>G

NM_000257.3(MYH7):c.2722C>G (p.Leu908Val)

NC_000014.9:g.23424107G>C

CM000676.2:g.23424107G>C

NC_000014.8:g.23893316G>C

CM000676.1:g.23893316G>C

NC_000014.7:g.22963156G>C

NG_007884.1:g.16555C>G

NM_000257.4:c.2722C>G

ENST00000355349.3:c.2722C>G

Pathogenic

PP1_Strong PM2 PM1 PS4 PP3

Evidence Links 5

Expert Panel

Cardiomyopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Cardiomyopathy VCEP

The c.2722C>G (p.Leu908Val) variant in MYH7 has been reported in >20 individuals with hypertrophic cardiomyopathy (PS4; PMID:1638703; PMID:8483915 PMID:12473556; PMID:12975413; PMID:27532257; Partners LMM ClinVar SCV000059471.5; AGCMC Sydney ClinVar SCV000692499.1; SHaRe consortium, PMID: 30297972). This variant segregated with disease in >20 affected individuals (PP1_Strong; PMID:1638703; PMID:8483915; Partners LMM ClinVar SCV000059471.5). 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; PP1_ Strong; PM1; PM2; PP3

PP1_Strong

>20 segregations including ClinVar SCV000059471.5

Variant segregated with disease in 5 affected family members PubMed:8483915

Variant segregated with disease in 18 affected family members PubMed:1638703

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 probands with HCM including ClinVar SCV000059471.5; ClinVar SCV000692499.1; SHaRe data

Variant identified in 5 probands with HCM PubMed:27532257

Variant identified in 3 probands with HCM PubMed:12473556

Variant identified in 1 proband with HCM PubMed:8483915

Variant identified in 1 proband with HCM PubMed:1638703

Variant identified in 3 probands with HCM PubMed:12975413

PP3

Tools predict damaging

Approved on: 2016-12-15

Published on: 2018-11-16

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