ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.5588C>T (p.Thr1863Met) (rs770863319)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000618427 SCV000738019 uncertain significance Cardiovascular phenotype 2017-05-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724909 SCV000332334 uncertain significance not provided 2015-06-29 criteria provided, single submitter clinical testing
GeneDx RCV000724909 SCV000235116 uncertain significance not provided 2017-05-08 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the RYR2 gene. The T1863M variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The T1863M variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Nevertheless, this substitution occurs at a position not conserved. Moreover, in silico analysis predicts this variant likely does not alter the protein structure/function. Furthermore, the T1863M variant is not located in one of the three hot-spot regions of the RYR2 gene, where the majority of pathogenic missense variants occur (Medeiros-Domingo et al., 2009). Additionally, no missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with an RYR2-related disorder (Stenson et al., 2014).
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000182732 SCV000740442 uncertain significance not specified 2016-09-26 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.