ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.50G>T (p.Arg17Leu)

dbSNP: rs746646172
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
Labcorp Genetics (formerly Invitae), Labcorp RCV001364187 SCV001560322 uncertain significance Hypertrophic cardiomyopathy 14 2023-06-15 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 17 of the MYH6 protein (p.Arg17Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with left ventricular noncompaction (PMID: 30471092). ClinVar contains an entry for this variant (Variation ID: 1055507). 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 expected to disrupt MYH6 protein function. 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.
GeneDx RCV001751720 SCV001994933 uncertain significance not provided 2020-03-27 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Identified in a cohort of individuals undergoing genetic testing for left ventricular noncompaction in published literature, but the number of patients with the variant, additional clinical information, and familial segregation information were not included (Richard et al., 2019); This variant is associated with the following publications: (PMID: 30471092)
PreventionGenetics, part of Exact Sciences RCV004528485 SCV004105582 uncertain significance MYH6-related disorder 2023-08-13 criteria provided, single submitter clinical testing The MYH6 c.50G>T variant is predicted to result in the amino acid substitution p.Arg17Leu. This variant was reported in an individual with left ventricular non compaction (Table S2, Cambon-Viala et al. 2021. PubMed ID: 34088380). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Additionally, different missense variants affecting the residue (p.Arg17Cys, p.Arg17His) have been reported in individuals with MYH6-related disease (Posch et al. 2011. PubMed ID: 22194935; Cuenca et al. 2016. PubMed ID: 26899768). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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.