ClinVar Miner

Submissions for variant NM_053025.4(MYLK):c.1613G>A (p.Arg538Gln)

gnomAD frequency: 0.00004  dbSNP: rs368509953
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000229195 SCV000291190 uncertain significance Aortic aneurysm, familial thoracic 7 2024-01-04 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 538 of the MYLK protein (p.Arg538Gln). This variant is present in population databases (rs368509953, gnomAD 0.03%). 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: 241752). 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.
GeneDx RCV000489548 SCV000576893 likely benign not provided 2019-08-12 criteria provided, single submitter clinical testing
Ambry Genetics RCV003380527 SCV004088744 likely benign Familial thoracic aortic aneurysm and aortic dissection 2023-07-08 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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