ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.14849A>G (p.Glu4950Gly)

dbSNP: rs1057517873
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 RCV000414217 SCV000490932 likely pathogenic not provided 2015-04-15 criteria provided, single submitter clinical testing The E4950G variant has not been published asa pathogenic variant or been reported as a benign polymorphism to our knowledge. The E4950G variant was notobserved in approximately 5900 individuals of European and African American ancestry in the NHLBI ExomeSequencing Project, indicating it is not a common benign variant in these populations. The E4950G variant is anon-conservative amino acid substitution, which is likely to impact secondary protein structure as theseresidues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that isconserved by class across species. In silico analysis is inconsistent in its predictions as to whether or not thevariant is damaging to the protein structure/function. However, The E4950G variant is located in a pathogenic varianthot spot" region of the RYR2 gene (Medeiros-Domingo et al., 2009). Furthermore, a missense variant in thesame residue (E4950K) and nearby residue (R4959Q) have been reported in the Human Gene MutationDatabase in association with RYR2-related arrhythmia (Stenson et al., 2014), supporting the functionalimportance of this region of the protein. Therefore, this variant is a strong candidate for a pathogenic variant, however the possibility that it is abenign 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.