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]

Variant: NM_000257.3(MYH7):c.2513C>T (p.Pro838Leu)

Curation History

CA012515

42910 (ClinVar)

Gene: MYH7

Condition: restrictive cardiomyopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: f43eef48-e44b-4436-b419-aee39de7c831

Approved on: 2016-12-15

Published on: 2018-11-16

HGVS expressions

NM_000257.3:c.2513C>T

NM_000257.3(MYH7):c.2513C>T (p.Pro838Leu)

NM_000257.4:c.2513C>T

ENST00000355349.3:c.2513C>T

NC_000014.9:g.23424935G>A

CM000676.2:g.23424935G>A

NC_000014.8:g.23894144G>A

CM000676.1:g.23894144G>A

NC_000014.7:g.22963984G>A

NG_007884.1:g.15727C>T

Pathogenic

PS2 PP3 PM2 PM1 PS4_Supporting

Evidence Links 2

Expert Panel

Cardiomyopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Cardiomyopathy VCEP

The c.2513C>T (p.Pro838Leu) variant in MYH7 has been reported as a de novo occurrence in two individuals with restrictive cardiomyopathy (PS4_Supporting and PS2: PMID:18380764; Partners LMM ClinVar SCV000059450.5). 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 restrictive cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (PMID:29300372): PS2; PM1; PM2; PP3; PS4_ Supporting

PS2

2 de novo occurrences, including ClinVar SCV000059450.5

Variant identified de novo in case with RCM PubMed:18380764

PP3

Tools predict damaging

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_Supporting

2 probands with RCM, including ClinVar SCV000059450.5

Variant identified in case with RCM PubMed:18380764

Curation History

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