ClinVar Miner

Submissions for variant NM_002474.3(MYH11):c.5787-4705C>A (rs765457680)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000232249 SCV000285804 uncertain significance Aortic aneurysm, familial thoracic 4 2015-12-06 criteria provided, single submitter clinical testing This sequence change replaces glutamine with lysine at codon 1941 of the MYH11 protein (p.Gln1941Lys). The glutamine residue is weakly conserved and there is a small physicochemical difference between glutamine and lysine. This variant is present in population databases (ExAC <0.01%) but has not been reported in the literature. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this is a rare missense change that is not predicted to affect protein function or cause disease. However, the evidence is insufficient at this time to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000520736 SCV000616968 uncertain significance not provided 2017-07-11 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the MYH11 gene. The Q1934K variant has not been published as pathogenic or been reported as benign to our knowledge. The Q1934K variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution occurs at a position that is conserved across species. The Q1934K variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Furthermore, in silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, the Q1934K variant occurs in an alternate transcript of the MYH11 gene where no variants have been reported in association with disease in the Human Gene Mutation Database (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Color RCV001187623 SCV001354474 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2020-04-29 criteria provided, single submitter clinical testing

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