Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000813293 | SCV000953649 | uncertain significance | RYR1-related disorder | 2021-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with aspartic acid at codon 4539 of the RYR1 protein (p.Gly4539Asp). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and aspartic acid. 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. 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: "Not Available"; 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, |
RCV002495137 | SCV002782563 | 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 | 2021-09-01 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV003514417 | SCV004358214 | uncertain significance | Malignant hyperthermia, susceptibility to, 1 | 2023-04-19 | criteria provided, single submitter | clinical testing | This missense variant replaces glycine with aspartic acid at codon 4539 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 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. |
| All of Us Research Program, |
RCV003514417 | SCV004816239 | uncertain significance | Malignant hyperthermia, susceptibility to, 1 | 2023-04-27 | criteria provided, single submitter | clinical testing |