ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.6027T>G (p.Ile2009Met) (rs1553529773)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000529143 SCV000637581 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 2017-07-04 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with methionine at codon 2009 of the RYR2 protein (p.Ile2009Met). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with a RYR2-related disease. This variant does not occur within one of the three regions of the RYR2 gene (N-terminal domain, central domain, or channel region) where other pathogenic variants have been reported to cluster (PMID: 19926015). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Integrated Genetics/Laboratory Corporation of America RCV000587864 SCV000697625 uncertain significance not provided 2016-10-13 criteria provided, single submitter clinical testing Variant summary: The RYR2 c.6027T>G (p.Ile2009Met) variant involves the alteration of a non- conserved nucleotide and 4/5 in silico tools predicting a benign outcome. The variant is absent from control dataset of ExAC (120306 chrs tested) and has not, to our knowledge, been reported in affected individuals via published reports or cited by a reputable database/clinical laboratory. Taking together, the variant was classified as VUS.

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.