ClinVar Miner

Submissions for variant NM_002474.3(MYH11):c.5213T>C (p.Ile1738Thr) (rs794729642)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Division of Human Genetics,Children's Hospital of Philadelphia RCV000185544 SCV000238423 uncertain significance Aortic aneurysm, familial thoracic 4 2015-03-24 no assertion criteria provided research This variant (c.5234T>C) is classified as a variant of uncertain significance (VUS) because it has not previously been reported in literature and does not occur in a large database of control samples (ExAC 0.3). Computational evidence is suggestive of a pathogenic variant. It is located in highly conserved nucleotide and amino acid positions and occurs in the myosin tail functional domain according to InterPro. Furthermore, the amino acid substitution involves a change from isoleucine to threonine, which is not a conservative alteration.
Invitae RCV000185544 SCV000543702 uncertain significance Aortic aneurysm, familial thoracic 4 2016-08-11 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 1745 of the MYH11 protein (p.Ile1745Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a MYH11-related disease. ClinVar contains an entry for this variant (Variation ID: 203373). 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 disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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