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.2156G>A (p.Arg719Gln)

CA011785

14107 (ClinVar)

Gene: MYH7

Condition: hypertrophic cardiomyopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 3a4b002a-d683-41f1-9f5f-3211c2a7f950

HGVS expressions

NM_000257.3:c.2156G>A

NM_000257.3(MYH7):c.2156G>A (p.Arg719Gln)

NM_000257.4:c.2156G>A

ENST00000355349.3:c.2156G>A

NC_000014.9:g.23425970C>T

CM000676.2:g.23425970C>T

NC_000014.8:g.23895179C>T

CM000676.1:g.23895179C>T

NC_000014.7:g.22965019C>T

NG_007884.1:g.14692G>A

Pathogenic

PS4 PP3 PM2 PM5 PM1 PP1_Strong

Evidence Links 6

Expert Panel

Cardiomyopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Cardiomyopathy VCEP

The c.2156G>A (p.Arg719Gln) variant in MYH7 has been reported in >30 individuals with hypertrophic cardiomyopathy (PS4; PMID:7848441; PMID:16199542; PMID:15358028; PMID:18411228; Partners LMM ClinVar SCV000059421.5; AGCMC Sydney ClinVar SCV000212634.1; SHaRe consortium, PMID: 30297972). This variant segregated with disease in 7 affected individuals (PP1_Strong; PMID:7848441; Partners LMM ClinVar SCV000059421.5). 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). A different pathogenic missense variant has been previously identified at this codon which may indicate that this residue is critical to the function of the protein (PM5; c.2155C>T p.Arg719Trp ClinVar Variation ID 14104). 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; PM5; PP3

PS4

>30 probands with HCM including SHaRe data, ClinVar SCV000059421.5 and ClinVar SCV000212634.1

Variant identified in 1 proband with HCM PubMed:18411228

Variant identified in1 proband with HCM PubMed:16199542

Variant identified in 3 probands with HCM PubMed:15358028

Variant identified in 1 proband with HCM PubMed:7848441

Variant identified in 2 probands with HCM PubMed:15858117

PP3

Tools predict damaging

PM2

Absent from ExAC

PM5

c.2155C>T (p.Arg719Trp) - Variation ID 14104 - Pathogenic by Expert Panel

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

PP1_Strong

7 segregations including ClinVar SCV000059421.5

Variant segregated with disease in 3 affected family members PubMed:7848441

Approved on: 2016-12-15

Published on: 2018-11-16

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