ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.11965A>C (p.Asn3989His) (rs794728779)

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 RCV000182803 SCV000235189 pathogenic not provided 2014-12-09 criteria provided, single submitter clinical testing p.Asn3989His (AAT>CAT): c.11965 A>C in exon 90 of the RYR2 gene (NM_001035.2). The Asn3989His mutation in the RYR2 gene has not been reported previously as a disease-causing mutation or as a benign polymorphism, to our knowledge. Asn3989His results in a non-conservative amino acid substitution of a neutral, polar Asparagine with a positively charged Histidine at a residue that is conserved across species. The Asn3989His mutation is located in the channel region mutation hot spot, where other mutations in nearby codons (Met3978Ile, Val3990Asp) have been reported in association with CPVT (Medeiros-Domingo A et al., 2009). Additionally, a mutation at this codon (Asn3989Asp) has been seen as an apparently de novo mutation in one patient tested for arrhythmia at GeneDx, further supporting the functional importance of this codon. In summary, Asn3989His in the RYR2 gene is interpreted as 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.