ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.5500C>T (p.Arg1834Cys)

gnomAD frequency: 0.00002  dbSNP: rs137923514
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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 RCV001040196 SCV001203757 uncertain significance Hypertrophic cardiomyopathy 14 2019-01-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 1834 of the MYH6 protein (p.Arg1834Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MYH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 312842). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 RCV001566648 SCV001790206 uncertain significance not provided 2020-07-20 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 312842; Landrum et al., 2016); 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 RCV004021579 SCV005018869 uncertain significance Cardiovascular phenotype 2024-02-12 criteria provided, single submitter clinical testing The p.R1834C variant (also known as c.5500C>T), located in coding exon 34 of the MYH6 gene, results from a C to T substitution at nucleotide position 5500. The arginine at codon 1834 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration has been reported in a hypertrophic cardiomyopathy (HCM) cohort (O'Hare BJ et al. Circ Genom Precis Med, 2020 Dec;13:e003013). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear.

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