ClinVar Miner

Submissions for variant NM_053025.4(MYLK):c.2629G>A (p.Val877Met)

gnomAD frequency: 0.00013  dbSNP: rs34542174
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000351703 SCV000337495 uncertain significance not provided 2015-11-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV002314013 SCV000739337 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2017-06-05 criteria provided, single submitter clinical testing The p.V877M variant (also known as c.2629G>A), located in coding exon 15 of the MYLK gene, results from a G to A substitution at nucleotide position 2629. The valine at codon 877 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is well 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 RCV000648725 SCV000770546 uncertain significance Aortic aneurysm, familial thoracic 7 2023-12-12 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 877 of the MYLK protein (p.Val877Met). This variant is present in population databases (rs34542174, gnomAD 0.02%). 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: 284753). 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.
CeGaT Center for Human Genetics Tuebingen RCV000351703 SCV001748079 uncertain significance not provided 2021-04-01 criteria provided, single submitter clinical testing
GeneDx RCV000351703 SCV001765034 uncertain significance not provided 2019-04-03 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar but additional evidence is not available (ClinVar Variant ID# 284753; Landrum et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003323492 SCV004029798 likely benign not specified 2023-07-21 criteria provided, single submitter clinical testing

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