ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.14104T>C (p.Trp4702Arg)

dbSNP: rs2145874187
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
GeneDx RCV001733441 SCV001983827 likely pathogenic not provided 2024-07-01 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 20681998, 33767344, 27535533)
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV001775183 SCV002012494 uncertain significance Congenital multicore myopathy with external ophthalmoplegia 2021-09-16 criteria provided, single submitter research ACMG codes: PM2; PP3
Labcorp Genetics (formerly Invitae), Labcorp RCV002543912 SCV003248824 uncertain significance RYR1-related disorder 2022-12-05 criteria provided, single submitter clinical testing 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 RYR1 protein function. This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 4702 of the RYR1 protein (p.Trp4702Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1301434). 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.