ClinVar Miner

Submissions for variant NM_053025.4(MYLK):c.1613G>A (p.Arg538Gln) (rs368509953)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489548 SCV000576893 uncertain significance not provided 2017-04-17 criteria provided, single submitter clinical testing The R538Q variant in the MYLK gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R538Q variant is observed in 4/16380 (0.024%) alleles from individuals of South Asian background, in the ExAC dataset (Lek et al., 2016). The R538Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, this substitution occurs at a position that is not conserved, and in silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, we interpret R538Q as a variant of uncertain significance.
Invitae RCV000229195 SCV000291190 uncertain significance Aortic aneurysm, familial thoracic 7 2015-12-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 538 of the MYLK protein (p.Arg538Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs368509953, ExAC 0.02%) but has not been reported in the literature. The glutamine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. In addition, algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, However, algorithms developed to predict the effect of missense changes on mRNA splicing suggest that this variant may alter mRNA splicing, but these predictions have not been confirmed by published transcriptional studies. In summary, this is a rare missense change that is not predicted to affect protein function and with uncertain impact on splicing. However the evidence is insufficient at this time to prove that conclusively. It has been classified as a Variant of Uncertain Significance.

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