ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.2384G>A (p.Arg795Gln)

gnomAD frequency: 0.00004  dbSNP: rs267606907
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000015210 SCV000960130 uncertain significance Hypertrophic cardiomyopathy 14 2024-07-03 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 795 of the MYH6 protein (p.Arg795Gln). This variant is present in population databases (rs267606907, gnomAD 0.06%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 11815426, 33407484). ClinVar contains an entry for this variant (Variation ID: 14147). 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 with a positive 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 RCV002453263 SCV002737723 uncertain significance Cardiovascular phenotype 2021-09-29 criteria provided, single submitter clinical testing The p.R795Q variant (also known as c.2384G>A), located in coding exon 18 of the MYH6 gene, results from a G to A substitution at nucleotide position 2384. The arginine at codon 795 is replaced by glutamine, an amino acid with highly similar properties. This variant was reported in one individual from a late onset hypertrophic cardiomyopathy (HCM) cohort, as well as in an exome cohort with cardiovascular details not provided (Niimura H et al. Circulation, 2002 Jan;105:446-51; Whiffin N et al. Genet Med, 2017 10;19:1151-1158). 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 RCV002504791 SCV002816298 uncertain significance Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to 2021-09-10 criteria provided, single submitter clinical testing
GeneDx RCV003125831 SCV003803517 uncertain significance not provided 2023-02-08 criteria provided, single submitter clinical testing Identified in patients with HCM in published literature (Niimura et al., 2002; Chung et al., 2021); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28518168, 33658040, 33407484, 11815426)
OMIM RCV000015210 SCV000035467 pathogenic Hypertrophic cardiomyopathy 14 2002-01-29 no assertion criteria provided literature only

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