ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.5627A>G (p.Lys1876Arg)

gnomAD frequency: 0.00033  dbSNP: rs201919534
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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 RCV000706086 SCV000835118 uncertain significance Hypertrophic cardiomyopathy 14 2023-10-24 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 1876 of the MYH6 protein (p.Lys1876Arg). This variant is present in population databases (rs201919534, gnomAD 0.07%), and has an allele count higher than expected for a pathogenic variant. 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: 582103). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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 RCV001592909 SCV001817021 uncertain significance not provided 2023-08-22 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function
Ambry Genetics RCV002343566 SCV002648476 uncertain significance Cardiovascular phenotype 2023-01-16 criteria provided, single submitter clinical testing The p.K1876R variant (also known as c.5627A>G), located in coding exon 35 of the MYH6 gene, results from an A to G substitution at nucleotide position 5627. The lysine at codon 1876 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002485768 SCV002788644 uncertain significance Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to 2021-07-26 criteria provided, single submitter clinical testing

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