ClinVar Miner

Submissions for variant NM_053025.4(MYLK):c.1957G>A (p.Glu653Lys)

gnomAD frequency: 0.00003  dbSNP: rs142765858
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000769337 SCV000739321 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2017-03-03 criteria provided, single submitter clinical testing The p.E653K variant (also known as c.1957G>A), located in coding exon 12 of the MYLK gene, results from a G to A substitution at nucleotide position 1957. The glutamic acid at codon 653 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000648712 SCV000770533 uncertain significance Aortic aneurysm, familial thoracic 7 2024-01-19 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 653 of the MYLK protein (p.Glu653Lys). This variant is present in population databases (rs142765858, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MYLK-related conditions. ClinVar contains an entry for this variant (Variation ID: 520001). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MYLK protein function with a negative predictive value of 80%. 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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000769337 SCV000900718 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2016-07-29 criteria provided, single submitter clinical testing
GeneDx RCV001559463 SCV001781693 uncertain significance not provided 2023-01-11 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function

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