ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.2629C>T (p.His877Tyr) (rs372575878)

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
GeneDx RCV000182701 SCV000235080 uncertain significance not provided 2014-07-02 criteria provided, single submitter clinical testing p.His877Tyr (CAT>TAT): c.2629 C>T in exon 23 of the RYR2 gene (NM_001035.2). The H877Y variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The H877Y variant was not observed with any significant frequency in approximately 5,900 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The H877Y 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. This substitution occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. In addition, the H877Y variant is not located in any of the mutation hot spot" regions in the RYR2 gene (Medeiros-Domingo A et al., 2009), and no mutations in nearby residues have been reported in association with cardiomyopathy, indicating this region of the protein may be tolerant of change. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in CARDIOMYOPATHY,ARVC panel(s)."
Ambry Genetics RCV000619081 SCV000737831 uncertain significance Cardiovascular phenotype 2019-04-09 criteria provided, single submitter clinical testing Insufficient evidence
Invitae RCV000639124 SCV000760686 likely benign Catecholaminergic polymorphic ventricular tachycardia 2019-12-18 criteria provided, single submitter clinical testing
Color RCV001189147 SCV001356372 uncertain significance Cardiomyopathy 2019-12-09 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.