ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.2065G>A (p.Glu689Lys)

gnomAD frequency: 0.00001  dbSNP: rs144845360
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
Labcorp Genetics (formerly Invitae), Labcorp RCV000821155 SCV000961902 uncertain significance RYR1-related disorder 2021-08-24 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 689 of the RYR1 protein (p.Glu689Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs144845360, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 RCV002495173 SCV002786789 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 2021-10-19 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV003489914 SCV004236871 uncertain significance not provided 2023-04-26 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004002830 SCV004841363 uncertain significance Malignant hyperthermia, susceptibility to, 1 2023-12-01 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with lysine at codon 689 of the RYR1 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 RYR1-related disorders in the literature. This variant has been identified in 4/250416 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 RCV004029061 SCV004945822 uncertain significance Inborn genetic diseases 2024-01-24 criteria provided, single submitter clinical testing The c.2065G>A (p.E689K) alteration is located in exon 18 (coding exon 18) of the RYR1 gene. This alteration results from a G to A substitution at nucleotide position 2065, causing the glutamic acid (E) at amino acid position 689 to be replaced by a lysine (K). 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.