ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.7385C>T (p.Pro2462Leu) (rs794728757)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182762 SCV000235147 likely pathogenic not provided 2012-07-31 criteria provided, single submitter clinical testing p.Pro2462Leu (CCA>CTA): c.7385 C>T in exon 49 of the RYR2 gene (NM_001035.2). The Pro2462Leu variant in the RYR2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Pro2462Leu results in a non-conservative amino acid substitution of one non-polar residue for another at a position that is conserved across species. In silico analysis predicts Pro2462Leu is probably damaging to the protein structure/function. Mutations in nearby residues (Arg2474Ser, Val2475Phe) have been reported in association with CPVT, further supporting the functional importance of this region of the protein. Furthermore, the NHLBI ESP Exome Variant Server reports Pro2462Leu was not observed in approximately 6,000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. In summary, while Pro2462Leu is a good candidate for a disease-causing mutation, with the clinical and molecular information available at this time we cannot unequivocally determine the clinical significance of this variant. The variant is found in CPVT panel(s).

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.