ClinVar Miner

Submissions for variant NM_053025.4(MYLK):c.3184G>T (p.Ala1062Ser) (rs11558550)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000494597 SCV000583322 uncertain significance not provided 2017-05-18 criteria provided, single submitter clinical testing The A1062S variant in the MYLK gene has been previously reported in an individual with sporadic abdominal aortic aneurysm, who also harbored a variant of uncertain significance in the FBN1 gene (van de Luijtgaarden et al., 2015). Of note, van de Luijtgaarden et al. (2015) classified A1062S as a likely benign variant on the basis of 0/5 in silico models predicting a deleterious protein effect. A1062S is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A1062S 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, this substitution occurs at a position that is not conserved, where S1062 is the wild-type residue in at least one species. Furthermore, in silico analysis predicts this variant likely does not alter the protein structure/function.
Invitae RCV000648724 SCV000770545 uncertain significance Aortic aneurysm, familial thoracic 7 2017-10-02 criteria provided, single submitter clinical testing This sequence change replaces alanine with serine at codon 1062 of the MYLK protein (p.Ala1062Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. This variant is present in population databases (rs11558550, ExAC 0.01%). This variant has been reported in an individual affected with aortic aneurysm (PMID: 26017485). ClinVar contains an entry for this variant (Variation ID: 375866). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
CSER_CC_NCGL; University of Washington Medical Center RCV000417348 SCV000503565 uncertain significance Familial aortic aneurysms 2016-08-01 no assertion criteria provided research Found in patient having exome sequencing for an unrelated indication. No known history of aortic aneurysm(s).

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