ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.13328+3A>G

gnomAD frequency: 0.00001  dbSNP: rs776115513
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001189032 SCV001356226 uncertain significance Cardiomyopathy 2019-04-15 criteria provided, single submitter clinical testing This variant is located near the intron 91 splice donor site of the RYR2 gene. Computational splicing tools predict that this variant may have a significant impact on 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 has been identified in 2/195046 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV001195400 SCV001365750 uncertain significance not specified 2019-04-17 criteria provided, single submitter clinical testing The c.13328+3A>G variant in RYR2 has not been previously reported in individuals with CPVT or ARVC but has been identified in 2/82156 European chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant is located in the 5' splice region. Computational tools predict a possible splicing impact, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the this variant is uncertain. ACMG/AMP Criteria applied: PM2, PP3.
Breakthrough Genomics, Breakthrough Genomics RCV004691382 SCV005186379 uncertain significance not provided criteria provided, single submitter not provided
All of Us Research Program, National Institutes of Health RCV004803535 SCV005428136 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 2024-08-06 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV005093973 SCV005813557 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 1 2024-08-07 criteria provided, single submitter clinical testing This sequence change falls in intron 91 of the RYR2 gene. It does not directly change the encoded amino acid sequence of the RYR2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs776115513, gnomAD 0.002%). This variant has been observed in individual(s) with sudden death (PMID: 33919104). ClinVar contains an entry for this variant (Variation ID: 926436). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.

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.