ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.481G>A (p.Ala161Thr)

gnomAD frequency: 0.00002  dbSNP: rs754736798
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483587 SCV000573483 uncertain significance not provided 2021-05-03 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# 423749; Landrum et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Labcorp Genetics (formerly Invitae), Labcorp RCV000647074 SCV000768861 uncertain significance Hypertrophic cardiomyopathy 14 2024-05-11 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 161 of the MYH6 protein (p.Ala161Thr). This variant is present in population databases (rs754736798, gnomAD 0.006%). 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: 423749). 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.
Fulgent Genetics, Fulgent Genetics RCV002475952 SCV002794375 uncertain significance Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to 2021-08-19 criteria provided, single submitter clinical testing
Ambry Genetics RCV004984907 SCV005451673 uncertain significance Cardiovascular phenotype 2024-10-17 criteria provided, single submitter clinical testing The p.A161T variant (also known as c.481G>A), located in coding exon 3 of the MYH6 gene, results from a G to A substitution at nucleotide position 481. The alanine at codon 161 is replaced by threonine, an amino acid with 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. Based on the available evidence, the clinical significance of this variant remains unclear.

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