ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.13822C>T (p.Arg4608Trp) (rs794728799)

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 RCV000182840 SCV000235228 likely pathogenic not provided 2015-04-15 criteria provided, single submitter clinical testing p.Arg4608Trp (CGG>TGG): c.13822 C>T in exon 95 of the RYR2 gene (NM_001035.2). The R4608W variant in the RYR2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. The R4608W variant was not observed in approximately 6000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. R4608W is a non-conservative amino acid substitution as these residues differ in polarity, charge, size and/or other properties and is more likely to impact secondary structure. The R4608 residue is well conserved across species, and is located in the c-terminal channel region of the RYR2 gene (Medeiros-Domingo A et al., 2009). Mutations in nearby residues (A4607P, E4611K) have been reported in association with arrhythmia, supporting the functional significance of this region of the protein. Additionally, in silico analysis predicts R4608W is damaging to the protein structure/function. In summary, R4608W is a good candidate for a disease-causing mutation. 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.