ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.12002A>G (p.Asp4001Gly) (rs1064793256)

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 RCV000487006 SCV000565512 likely pathogenic not provided 2014-12-17 criteria provided, single submitter clinical testing A novel D4001G variant that is likely pathogenic was identified in the RYR2 gene. It has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The D4001G variant was not observed in approximately 6,000 individuals of European and African American ancestry in an external variant database, indicating it is not a common benign variant in these populations. The D4001G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, this substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, missense variantas in nearby residues (K3997E, M4002I) have been reported in the Human Gene Mutation Database (Stenson P. et al., 2014) and D4001G is located in a mutation hot spot" in the RYR2 gene (Medeiros-Domingo A et al., 2009). Therefore, this is a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded."

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.