ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.4192C>T (p.Arg1398Trp)

gnomAD frequency: 0.00002  dbSNP: rs374022661
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000820467 SCV000961182 uncertain significance Hypertrophic cardiomyopathy 14 2023-10-03 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1398 of the MYH6 protein (p.Arg1398Trp). This variant is present in population databases (rs374022661, gnomAD 0.01%). 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: 662744). 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. 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.
GeneDx RCV001772136 SCV001992272 uncertain significance not provided 2019-04-26 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 a deleterious effect
Ambry Genetics RCV002332703 SCV002628578 uncertain significance Cardiovascular phenotype 2022-03-08 criteria provided, single submitter clinical testing The p.R1398W variant (also known as c.4192C>T), located in coding exon 28 of the MYH6 gene, results from a C to T substitution at nucleotide position 4192. The arginine at codon 1398 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002501136 SCV002814968 uncertain significance Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to 2021-08-11 criteria provided, single submitter clinical testing

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