ClinVar Miner

Submissions for variant NM_053025.4(MYLK):c.593A>G (p.Asn198Ser) (rs201835018)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Human Genetics, Inc RCV000659933 SCV000781837 likely benign Connective tissue disorder 2016-11-01 criteria provided, single submitter clinical testing
GeneDx RCV000498107 SCV000590640 uncertain significance not specified 2017-06-15 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the MYLK gene. The N198S variant has not been published as pathogenic or been reported as benign to our knowledge. However, it has been observed in 10/66738 (0.015%) 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 N198S 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 serine (S) is the wild-type residue at this position in two mammalian species. Furthermore, in silico analysis predicts this variant likely does not alter the protein structure/function. Finally, this variant is also classified as a variant of uncertain significance in ClinVar by a different clinical laboratory (ClinVar SCV000291206.1; Landrum et al., 2016).
Invitae RCV000226549 SCV000291206 uncertain significance Aortic aneurysm, familial thoracic 7 2018-06-15 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 198 of the MYLK protein (p.Asn198Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs201835018, ExAC 0.01%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with MYLK-related disease. ClinVar contains an entry for this variant (Variation ID: 241764). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15". The serine 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.