ClinVar Miner

Submissions for variant NM_002474.3(MYH11):c.3895G>A (p.Ala1299Thr)

gnomAD frequency: 0.00001  dbSNP: rs1388360113
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000520475 SCV000618770 uncertain significance not provided 2017-06-28 criteria provided, single submitter clinical testing The A1299T variant in the MYH11 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The A1299T variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A1299T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret A1299T as a variant of uncertain significance.
Invitae RCV002527607 SCV003461093 uncertain significance Aortic aneurysm, familial thoracic 4 2024-01-04 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 1306 of the MYH11 protein (p.Ala1306Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MYH11-related conditions. ClinVar contains an entry for this variant (Variation ID: 450217). 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 not expected to disrupt MYH11 protein function with a negative predictive value of 95%. 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.

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