ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.4141G>A (p.Ala1381Thr)

gnomAD frequency: 0.00003  dbSNP: rs753774406
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000823137 SCV000963984 uncertain significance Hypertrophic cardiomyopathy 14 2024-12-08 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 1381 of the MYH6 protein (p.Ala1381Thr). This variant is present in population databases (rs753774406, 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: 664946). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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 RCV001731946 SCV001982666 uncertain significance not provided 2021-09-23 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 has a deleterious effect on protein structure/function; Reported in ClinVar but additional evidence is not available (ClinVar Variant ID# 664946; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 26582918)
Ambry Genetics RCV003169048 SCV003906713 uncertain significance Cardiovascular phenotype 2023-01-26 criteria provided, single submitter clinical testing The p.A1381T variant (also known as c.4141G>A), located in coding exon 27 of the MYH6 gene, results from a G to A substitution at nucleotide position 4141. The alanine at codon 1381 is replaced by threonine, an amino acid with 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.

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