ClinVar Miner

Submissions for variant NM_000258.2(MYL3):c.518T>A (p.Met173Lys) (rs730880962)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000158962 SCV000208897 pathogenic not provided 2011-11-01 criteria provided, single submitter clinical testing The Met173Lys mutation in the MYL3 gene has not been reported previously as a disease causing mutation or as a benign polymorphism, to our knowledge. However, another mutation affecting this same codon (Met173Val) has been reported in a patient with childhood onset HCM and it was absent from more than 1,000 control alleles (Morita et al. 2008). Met173Lys results in a non conservative amino acid substitution of a non polar Methionine with a polar Lysine at a position that is conserved throughout evolution. Furthermore, Met173Lys was not observed in up to 200 control alleles from individuals of Caucasian ancestry tested at GeneDx, indicating it is not a common benign polymorphism in this population. Mutations in MYL3 are rare in HCM, and have been reported in only about 1% of patients with an autosomal dominant familial form of the disease (Cirino A et al., 2011). The variant is found in HCM panel(s).
Invitae RCV000800210 SCV000939910 uncertain significance Hypertrophic cardiomyopathy 2018-09-28 criteria provided, single submitter clinical testing This sequence change replaces methionine with lysine at codon 173 of the MYL3 protein (p.Met173Lys). The methionine residue is moderately conserved and there is a moderate physicochemical difference between methionine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MYL3-related disease. ClinVar contains an entry for this variant (Variation ID: 181449). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.