ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.4535C>T (p.Ser1512Leu)

gnomAD frequency: 0.00001  dbSNP: rs763022972
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001314722 SCV001505266 uncertain significance Hypertrophic cardiomyopathy 14 2020-06-04 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with MYH6-related conditions. This variant is present in population databases (rs763022972, ExAC 0.01%). This sequence change replaces serine with leucine at codon 1512 of the MYH6 protein (p.Ser1512Leu). The serine residue is weakly conserved and there is a large physicochemical difference between serine and leucine.
GeneDx RCV001586122 SCV001811952 uncertain significance not provided 2019-06-14 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect
Ambry Genetics RCV004034324 SCV005018897 uncertain significance Cardiovascular phenotype 2023-10-28 criteria provided, single submitter clinical testing The p.S1512L variant (also known as c.4535C>T), located in coding exon 30 of the MYH6 gene, results from a C to T substitution at nucleotide position 4535. The serine at codon 1512 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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