ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.4684C>T (p.Arg1562Trp)

gnomAD frequency: 0.00004  dbSNP: rs756237624
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000534392 SCV000648269 uncertain significance Hypertrophic cardiomyopathy 14 2023-12-09 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 1562 of the MYH6 protein (p.Arg1562Trp). This variant is present in population databases (rs756237624, gnomAD 0.003%). 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: 470543). 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 RCV002341393 SCV002638189 uncertain significance Cardiovascular phenotype 2022-10-17 criteria provided, single submitter clinical testing The p.R1562W variant (also known as c.4684C>T), located in coding exon 31 of the MYH6 gene, results from a C to T substitution at nucleotide position 4684. The arginine at codon 1562 is replaced by tryptophan, an amino acid with dissimilar properties. This variant has been detected in a hypertrophic cardiomyopathy cohort; however, clinical details were limited (Mademont-Soler I et al. PLoS ONE, 2017 Aug;12:e0181465). 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.

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