ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.1955C>T (p.Ala652Val)

gnomAD frequency: 0.00004  dbSNP: rs757908433
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
Invitae RCV001052771 SCV001216996 uncertain significance RYR1-related disorder 2022-10-19 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 652 of the RYR1 protein (p.Ala652Val). This variant is present in population databases (rs757908433, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 848919). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RYR1 protein function. 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.
Fulgent Genetics, Fulgent Genetics RCV002497409 SCV002812230 uncertain significance Central core myopathy; Malignant hyperthermia, susceptibility to, 1; Congenital multicore myopathy with external ophthalmoplegia; Congenital myopathy with fiber type disproportion; King Denborough syndrome 2021-07-16 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV003130126 SCV003810503 uncertain significance not provided 2019-07-03 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV001052771 SCV004117218 uncertain significance RYR1-related disorder 2023-09-18 criteria provided, single submitter clinical testing The RYR1 c.1955C>T variant is predicted to result in the amino acid substitution p.Ala652Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0096% of alleles in individuals of Ashkenazi Jewish descent in gnomAD (http://gnomad.broadinstitute.org/variant/19-38948720-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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.