ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.1639A>G (p.Met547Val)

gnomAD frequency: 0.00004  dbSNP: rs760722098
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001764143 SCV002000453 uncertain significance not provided 2020-01-27 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function
Labcorp Genetics (formerly Invitae), Labcorp RCV001885063 SCV002138917 uncertain significance Hypertrophic cardiomyopathy 14 2024-10-16 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 547 of the MYH6 protein (p.Met547Val). This variant is present in population databases (rs760722098, gnomAD 0.03%). 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: 1314760). 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.
Ambry Genetics RCV002405308 SCV002709276 uncertain significance Cardiovascular phenotype 2022-12-25 criteria provided, single submitter clinical testing The p.M547V variant (also known as c.1639A>G), located in coding exon 13 of the MYH6 gene, results from an A to G substitution at nucleotide position 1639. The methionine at codon 547 is replaced by valine, an amino acid with highly similar properties. 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.
Fulgent Genetics, Fulgent Genetics RCV002489809 SCV002791211 uncertain significance Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to 2021-09-01 criteria provided, single submitter clinical testing

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