ClinVar Miner

Submissions for variant NM_002474.3(MYH11):c.5215G>A (p.Ala1739Thr) (rs1029371842)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000536102 SCV000641065 uncertain significance Aortic aneurysm, familial thoracic 4 2017-03-06 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 1746 of the MYH11 protein (p.Ala1746Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. While this variant is not present in population databases (ExAC no frequency), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with a MYH11-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
GeneDx RCV000658208 SCV000779979 uncertain significance not provided 2018-05-15 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the MYH11 gene. The A1739T variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016). The A1739T 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. However, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function.
Color RCV001178597 SCV001343075 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2019-08-26 criteria provided, single submitter clinical testing

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