ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.635C>T (p.Ala212Val)

gnomAD frequency: 0.00003  dbSNP: rs780456381
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000621731 SCV000736885 uncertain significance Cardiovascular phenotype 2022-07-22 criteria provided, single submitter clinical testing The p.A212V variant (also known as c.635C>T), located in coding exon 5 of the MYH6 gene, results from a C to T substitution at nucleotide position 635. The alanine at codon 212 is replaced by valine, an amino acid with similar properties. This alteration has been reported in a Wolff-Parkinson-White cohort, but clinical details were limited (Bowles NE et al. Am. J. Med. Genet. A. 2015;167A:2975-84). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV000624414 SCV000740623 likely benign not specified 2017-04-24 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000701024 SCV000829805 uncertain significance Hypertrophic cardiomyopathy 14 2024-10-14 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 212 of the MYH6 protein (p.Ala212Val). This variant is present in population databases (rs780456381, gnomAD 0.006%). This missense change has been observed in individual(s) with Wolff–Parkinson–White syndrome (PMID: 26284702). ClinVar contains an entry for this variant (Variation ID: 519020). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt MYH6 protein function with a negative predictive value of 80%. 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.

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