ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.5653G>T (p.Gly1885Trp)

dbSNP: rs200197527
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health RCV000171817 SCV000050829 benign not specified 2013-06-24 criteria provided, single submitter research
Color Diagnostics, LLC DBA Color Health RCV001180808 SCV001345829 uncertain significance Cardiomyopathy 2023-04-28 criteria provided, single submitter clinical testing This missense variant replaces glycine with tryptophan at codon 1885 of the RYR2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RYR2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The 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.
Ambry Genetics RCV002345583 SCV002651850 uncertain significance Cardiovascular phenotype 2021-08-20 criteria provided, single submitter clinical testing The p.G1885W variant (also known as c.5653G>T), located in coding exon 37 of the RYR2 gene, results from a G to T substitution at nucleotide position 5653. The glycine at codon 1885 is replaced by tryptophan, an amino acid with highly dissimilar properties. This alteration has been reported as a secondary cardiac variant in an exome cohort; however, clinical details are limited (Ng D et al. Circ Cardiovasc Genet, 2013 Aug;6:337-46). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health RCV003995654 SCV004820155 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 2023-08-15 criteria provided, single submitter clinical testing This missense variant replaces glycine with tryptophan at codon 1885 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 has not been identified 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.

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.