ClinVar Miner

Submissions for variant NM_053025.4(MYLK):c.619G>A (p.Val207Met) (rs756560698)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000617108 SCV000320433 uncertain significance Cardiovascular phenotype 2015-11-13 criteria provided, single submitter clinical testing Rarity in general population databases (dbsnp, esp, 1000 genomes);Insufficient or conflicting evidence
Illumina Clinical Services Laboratory,Illumina RCV000249352 SCV000440339 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000520122 SCV000620487 uncertain significance not provided 2017-08-31 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the MYLK gene. The V207M variant has not been published as pathogenic or been reported as benign to our knowledge. This variant has been observed in 2/16512 (0.012%) alleles from individuals of South Asian ancestry, and in 2/66740 (0.003%) alleles from individuals of Non-Finnish European ancestry, in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The V207M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Additionally, this substitution occurs at a position that is not conserved across species and in silico analysis predicts this variant likely does not alter the protein structure/function.
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000659934 SCV000781838 likely benign Connective tissue disease 2016-11-01 criteria provided, single submitter clinical testing
Invitae RCV001045808 SCV001209682 uncertain significance Aortic aneurysm, familial thoracic 7 2019-12-19 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 207 of the MYLK protein (p.Val207Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs756560698, ExAC 0.01%). This variant has not been reported in the literature in individuals with MYLK-related disease. ClinVar contains an entry for this variant (Variation ID: 264468). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15". The methionine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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