ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.4793C>T (p.Ser1598Leu)

gnomAD frequency: 0.00002  dbSNP: rs536807961
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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 RCV001898400 SCV002164456 uncertain significance Hypertrophic cardiomyopathy 14 2022-02-08 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. This variant has not been reported in the literature in individuals affected with MYH6-related conditions. This variant is present in population databases (rs536807961, gnomAD 0.003%). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1598 of the MYH6 protein (p.Ser1598Leu).
Fulgent Genetics, Fulgent Genetics RCV002482735 SCV002785936 uncertain significance Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to 2021-09-28 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV001898400 SCV005044827 uncertain significance Hypertrophic cardiomyopathy 14 criteria provided, single submitter clinical testing The missense c.4793C>T p.Ser1598Leu variant in MYH6 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Ser1598Leu is reported with an allele frequency of 0.002% in the gnomAD exomes database and is novel not in any individuals in 1000 Genomes database. This variant has been reported to the ClinVar database as Uncertain Significance. The amino acid change p.Ser1598Leu in MYH6 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Ser at position 1598 is changed to a Leu changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Variant of Uncertain Significance VUS.

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