ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.7793C>G (p.Ala2598Gly)

dbSNP: rs770719689
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
Invitae RCV001920413 SCV002186235 uncertain significance RYR1-related disorder 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces alanine with glycine at codon 2598 of the RYR1 protein (p.Ala2598Gly). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. 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 RCV002484459 SCV002791232 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 2021-08-26 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV003490933 SCV004236898 uncertain significance not provided 2023-02-15 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004010862 SCV004832307 uncertain significance Malignant hyperthermia, susceptibility to, 1 2023-11-30 criteria provided, single submitter clinical testing This missense variant replaces alanine with glycine at codon 2598 of the RYR1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RYR1-related disorders in the literature. This variant has been identified in 2/279822 chromosomes 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 RCV004671521 SCV005161775 uncertain significance Inborn genetic diseases 2024-06-02 criteria provided, single submitter clinical testing The c.7793C>G (p.A2598G) alteration is located in exon 48 (coding exon 48) of the RYR1 gene. This alteration results from a C to G substitution at nucleotide position 7793, causing the alanine (A) at amino acid position 2598 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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.