ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.5102G>A (p.Arg1701Gln)

gnomAD frequency: 0.00006  dbSNP: rs762103586
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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 RCV000647049 SCV000768836 uncertain significance Hypertrophic cardiomyopathy 14 2024-07-01 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 1701 of the MYH6 protein (p.Arg1701Gln). This variant is present in population databases (rs762103586, gnomAD 0.008%). 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: 537951). 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.
GeneDx RCV001766392 SCV001991469 uncertain significance not provided 2019-07-25 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 RCV002334165 SCV002644630 uncertain significance Cardiovascular phenotype 2024-04-01 criteria provided, single submitter clinical testing The p.R1701Q variant (also known as c.5102G>A), located in coding exon 32 of the MYH6 gene, results from a G to A substitution at nucleotide position 5102. The arginine at codon 1701 is replaced by glutamine, an amino acid with highly similar 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. This alteration has been reported in a subject with hypertrophic cardiomyopathy (HCM) who also had a variant in another cardiac-related gene (van Lint FHM et al. Neth Heart J, 2019 Jun;27:304-309). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002507108 SCV002812905 uncertain significance Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to 2021-09-14 criteria provided, single submitter clinical testing

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