ClinVar Miner

Submissions for variant NM_053025.4(MYLK):c.1474G>A (p.Ala492Thr) (rs143010767)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769341 SCV000900724 uncertain significance Thoracic aortic aneurysm and aortic dissection 2017-05-11 criteria provided, single submitter clinical testing
Center for Human Genetics, Inc RCV000680575 SCV000807990 likely benign Connective tissue disorder 2018-06-01 criteria provided, single submitter clinical testing
GeneDx RCV000603263 SCV000725151 likely benign not specified 2017-11-30 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000529711 SCV000650513 uncertain significance Aortic aneurysm, familial thoracic 7 2017-04-10 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 492 of the MYLK protein (p.Ala492Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs143010767, ExAC 0.08%) but has not been reported in the literature in individuals with a MYLK-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function, and is found in the population at an appreciable frequency. This variant is not anticipated to cause disease; however, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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