ClinVar Miner

Submissions for variant NM_002474.3(MYH11):c.4538T>A (p.Met1513Lys)

dbSNP: rs794728669
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182521 SCV000234867 uncertain significance not provided 2014-01-12 criteria provided, single submitter clinical testing p.Met1513Lys (M1513K) ATG>AAG: c.4538 T>A in exon 32 of the MYH11 gene (NM_002474.2). The M1513K variant in the MYH11 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. The M1513K variant is a non-conservative amino acid substitution as these residues differ in polarity, charge, size and/or other properties and is more likely to impact secondary structure. The M1513 residue is conserved across species. In silico analysis predicts M1513K is probably damaging to the protein structure/function. The M1513K variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. However, no mutations in nearby residues have been reported in association with TAAD or a related disorder suggesting this region of the protein may be tolerant to change. With the clinical and molecular information available at this time, we cannot definitively determine if M1513K is a disease-causing mutation or a rare benign variant. The variant is found in TAAD panel(s).
Invitae RCV002515315 SCV003335597 uncertain significance Aortic aneurysm, familial thoracic 4 2022-03-25 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 201077). This variant has not been reported in the literature in individuals affected with MYH11-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 1520 of the MYH11 protein (p.Met1520Lys).

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