ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.2335G>A (p.Glu779Lys)

dbSNP: rs1427104281
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Neuberg Centre For Genomic Medicine, NCGM RCV003320257 SCV002073262 uncertain significance Myosin storage myopathy criteria provided, single submitter clinical testing The missense variant p.E779K in MYH7 (NM_000257.4)has not been reported before as a pathogenic nor a benign variant. Another variant in the same position E779Q has been reported to be disease causing. The p.E779K variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The p.E779K missense variant is predicted to be damaging by both SIFT and PolyPhen2. The glutamic acid residue at codon 779 of MYH7 is conserved in all mammalian species. The nucleotide c.2335 in MYH7 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV002545196 SCV002977976 likely pathogenic Hypertrophic cardiomyopathy 2023-07-31 criteria provided, single submitter clinical testing 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. This variant is found within a region of MYH7 between codons 181 and 937 that contains the majority of the myosin head domain. Missense variants in this region have been shown to be significantly overrepresented in individuals with hypertrophic cardiomyopathy (PMID: 27532257). 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. ClinVar contains an entry for this variant (Variation ID: 1339203). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 779 of the MYH7 protein (p.Glu779Lys).

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