ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.3168G>C (p.Glu1056Asp)

gnomAD frequency: 0.00004  dbSNP: rs747198710
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV002525769 SCV000565289 uncertain significance not provided 2023-01-16 criteria provided, single submitter clinical testing Reported in an Egyptian individual with HCM, although detailed information was not provided (Kassem et al., 2013); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 21310275, 34542152, 23233322, 26582918)
Invitae RCV000700691 SCV000829458 uncertain significance Hypertrophic cardiomyopathy 2023-10-28 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 1056 of the MYH7 protein (p.Glu1056Asp). This variant is present in population databases (rs747198710, gnomAD 0.01%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (HCM) (PMID: 23233322). ClinVar contains an entry for this variant (Variation ID: 418362). 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 with a positive predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV002496850 SCV002800793 uncertain significance Hypertrophic cardiomyopathy 1; Myopathy, myosin storage, autosomal recessive; Myosin storage myopathy; Congenital myopathy with fiber type disproportion; Dilated cardiomyopathy 1S; MYH7-related skeletal myopathy 2021-10-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV003372725 SCV004079562 uncertain significance Cardiovascular phenotype 2023-07-20 criteria provided, single submitter clinical testing The p.E1056D variant (also known as c.3168G>C), located in coding exon 23 of the MYH7 gene, results from a G to C substitution at nucleotide position 3168. The glutamic acid at codon 1056 is replaced by aspartic acid, an amino acid with highly similar properties. This alteration has been reported in a hypertrophic cardiomyopathy (HCM) cohort; however, clinical details were limited (Kassem HSh et al. J Cardiovasc Transl Res, 2013 Feb;6:65-80). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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