ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.12541G>A (p.Gly4181Arg) (rs775477470)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000592307 SCV000704527 uncertain significance not provided 2017-01-06 criteria provided, single submitter clinical testing
Invitae RCV000705690 SCV000834699 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 2019-10-16 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 4181 of the RYR2 protein (p.Gly4181Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs775477470, ExAC 0.02%), 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 RYR2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but 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.
Fulgent Genetics,Fulgent Genetics RCV000765093 SCV000896302 uncertain significance Arrhythmogenic right ventricular dysplasia, familial, 2; Catecholaminergic polymorphic ventricular tachycardia type 1 2018-10-31 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000592307 SCV001147778 uncertain significance not provided 2019-03-01 criteria provided, single submitter clinical testing
Color RCV001189668 SCV001357004 uncertain significance Cardiomyopathy 2019-11-19 criteria provided, single submitter clinical testing

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.