ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.1265A>G (p.Tyr422Cys)

dbSNP: rs1891578725
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001752256 SCV001988288 uncertain significance not provided 2024-04-24 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV002032806 SCV002226755 uncertain significance Hypertrophic cardiomyopathy 14 2023-08-11 criteria provided, single submitter clinical testing 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. This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 422 of the MYH6 protein (p.Tyr422Cys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MYH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 1304489). 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 MYH6 protein function.
Ambry Genetics RCV002449410 SCV002681336 uncertain significance Cardiovascular phenotype 2023-11-05 criteria provided, single submitter clinical testing The p.Y422C variant (also known as c.1265A>G), located in coding exon 11 of the MYH6 gene, results from an A to G substitution at nucleotide position 1265. The tyrosine at codon 422 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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.

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