ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.12372C>A (p.Ser4124Arg) (rs771994461)

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 RCV000182816 SCV000235202 pathogenic not provided 2012-06-05 criteria provided, single submitter clinical testing p.Ser4124Arg (AGC>AGA): c.12372 C>A in exon 90 of the RYR2 gene (NM_001035.2). The Ser4124Arg mutation in the RYR2 gene has not been reported previously as a disease-causing mutation, nor as a benign polymorphism, to our knowledge. Ser4124Arg results in a semi-conservative amino acid substitution of a neutral, polar Serine residue with a positively charged Arginine residue. Located in the cytoplasmic I-domain RYR2 mutation hot spot, mutations at the same residue (Ser4124Gly, Ser4124Thr) as well as a nearby residue (Arg4144Cys) have been reported in association with CPVT, supporting the functional importance of this region of the protein. In addition, the NHLBI ESP Exome Variant Server reports Ser4124Arg was not observed in approximately 5,000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. In summary, Ser4124Arg in the RYR2 gene is interpreted to be a likely 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.