ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.4780G>A (p.Val1594Ile) (rs794728737)

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
GeneDx RCV000182727 SCV000235111 uncertain significance not provided 2012-06-04 criteria provided, single submitter clinical testing p.Val1594Ile (GTC>ATC): c.4780 G>A in exon 36 of the RYR2 gene (NM_001035.2). The Val1594Ile variant in the RYR2 gene has not been previously reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Val1594Ile results in a conservative amino acid substitution of one non-polar residue for another at a position that is not well-conserved in other species. In addition, the Val1594Ile variant is not located in any of the RYR2 mutation hot spots and no mutations in nearby codons have been reported, indicating this region may be tolerant of change (Medeiros-Domingo A et al., 2009). However, the NHLBI ESP Exome Variant Server reports Val1594Ile was not observed in approximately 5000 samples from individuals of European and African American backgrounds indicating it is not a common, benign variant in these populations. Therefore, the clinical significance of the Val1594Ile variant in the RYR2 gene is currently unknown. The variant is found in ARVC panel(s).
Color RCV000778053 SCV000914168 uncertain significance Cardiomyopathy 2018-10-05 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant is located in the cytoplasmic domain of the RYR2 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant is rare in the general population and has been identified in 1/244724 chromosomes by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.

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.