Variant: NM_000257.3(MYH7):c.5401G>A (p.Glu1801Lys)

CA016087

43069 (ClinVar)

Gene: MYH7

Condition: dilated cardiomyopathy

Inheritance Mode: Autosomal dominant inheritance

UUID: 7c729fe3-84ef-4174-a0d8-c152b6dc76d7

Approved on: 2016-12-15

Published on: 2018-11-16

HGVS expressions

NM_000257.3:c.5401G>A
NM_000257.3(MYH7):c.5401G>A (p.Glu1801Lys)
NC_000014.9:g.23415153C>T
CM000676.2:g.23415153C>T
NC_000014.8:g.23884362C>T
CM000676.1:g.23884362C>T
NC_000014.7:g.22954202C>T
NG_007884.1:g.25509G>A
NM_000257.4:c.5401G>A
ENST00000355349.3:c.5401G>A

Likely Pathogenic

• Met criteria codes: PP3 PM2 PM6 PS4_Supporting

Expert Panel

Cardiomyopathy VCEP

Criteria Specification Information

Evidence submitted by expert panel

Cardiomyopathy VCEP

The c.5401G>A (p.Glu1801Lys) variant in MYH7 has been reported in 4 individuals with dilated cardiomyopathy, one of whom had additional myopathy features (PS4_Supporting; PMID:19477645; Partners LMM ClinVar SCV000059616.5). Additionally, in two of the probands with dilated cardiomyopathy, the variant occurred de novo (PM6; Partners LMM ClinVar SCV000059616.5). This variant was absent from large population studies (PM2; http://exac.broadinstitute.org). 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 likely pathogenic for dilated cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (PMID:29300372): PM2; PM6; PP3; PS4_ Supporting

Met criteria codes

• PP3: Tools predict damaging
• PM2: Absent from ExAC
• PM6: 2 assumed de novo occurrences (from ClinVar SCV000059616.5)
• PS4_Supporting: 4 cases with DCM identified, one of which has myopathy features (including ClinVar SCV000059616.5)