ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.1969A>C (p.Lys657Gln)

dbSNP: rs727503264
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000811264 SCV000199215 likely pathogenic Hypertrophic cardiomyopathy 2013-11-15 criteria provided, single submitter clinical testing The Lys657Gln variant in MYH7 has now been identified in 1 Caucasian adult with HCM and segregated with disease in 3 affected relatives. It has not been identi fied in large population studies. Lysine (Lys) at position 657 is highly conserv ed in mammals and across evolutionarily distant species and the change to glutam ine (Gln) was predicted to be pathogenic using a computational tool clinically v alidated by our laboratory. This tool's pathogenic prediction is estimated to be correct 94% of the time (Jordan 2011). In summary, this variant is likely to be pathogenic, though additional studies are required to fully establish its clini cal significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000811264 SCV000951522 likely pathogenic Hypertrophic cardiomyopathy 2022-11-29 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 26337809, 27532257). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 164351). This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 657 of the MYH7 protein (p.Lys657Gln). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYH7 protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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