Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000538281 | SCV000659986 | uncertain significance | RYR1-related disorder | 2022-08-22 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 2092 of the RYR1 protein (p.Arg2092Trp). This variant is present in population databases (rs772164452, gnomAD 0.006%). 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: 478251). 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: "Benign"; 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. |
Prevention |
RCV000721604 | SCV000852701 | uncertain significance | not provided | 2018-03-22 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002483517 | SCV002778006 | 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 | 2021-10-12 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV003999506 | SCV004815989 | uncertain significance | Malignant hyperthermia, susceptibility to, 1 | 2023-12-13 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with tryptophan at codon 2092 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 8/239776 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. |