ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.12217G>A (p.Asp4073Asn) (rs768341298)

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 RCV000182808 SCV000235194 uncertain significance not provided 2014-05-29 criteria provided, single submitter clinical testing p.Asp4073Asn (GAT>AAT): c.12217 G>A in exon 90 of the RYR2 gene (NM_001035.2). The D4073N variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The D4073N variant was not observed in approximately 6,200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The D4073N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved when present across species. Another missense mutation in a nearby residue (E4076K) has been reported in association with polymorphic ventricular tachycardia, supporting the functional importance of this region of the protein. Furthermore, D4073N is located in the channel region, a mutation hot-spot" of the RYR2 gene (Medeiros-Domingo A et al., 2009). Nevertheless, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. 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 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.