Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Prevention |
RCV000119545 | SCV000852447 | pathogenic | not provided | 2017-06-19 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001046476 | SCV001210381 | pathogenic | RYR1-related disorder | 2023-10-03 | 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 4893 of the RYR1 protein (p.Arg4893Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant RYR1-related myopathies (PMID: 11709545, 14670767, 15299003, 24950660). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 65989). 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 expected to disrupt RYR1 protein function. Experimental studies have shown that this missense change affects RYR1 function (PMID: 12642598, 15175001, 23308296, 24950660). For these reasons, this variant has been classified as Pathogenic. |
| Revvity Omics, |
RCV000119545 | SCV002019956 | pathogenic | not provided | 2021-10-20 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV002496742 | SCV002796934 | likely pathogenic | Central core myopathy; Malignant hyperthermia, susceptibility to, 1; Congenital multicore myopathy with external ophthalmoplegia; Congenital myopathy with fiber type disproportion; King Denborough syndrome | 2022-01-17 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV003996489 | SCV004842068 | 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 4893 of the RYR1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function. This variant occurs in a region of the RYR1 protein that is considered to be a hotspot for pathogenic variants that contribute to malignant hyperthermia susceptibility (PMID: 21118704). Functional studies have shown that this variant showed reduced calcium sensitivity and release in response to RYR1 agonists and voltage compared to wild-type (PMID: 12642598, 15175001, 15299003, 23308296). This variant has not been reported in individuals affected with autosomal dominant malignant hyperthermia in the literature, although it is associated with other phenotype(s) (ClinVar variation ID: 65989). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Due to insufficient evidence, this variant is classified as a Variant of Uncertain Significance for autosomal dominant malignant hyperthermia. |
| Gene |
RCV000056236 | SCV000087325 | pathologic | Central core myopathy | 2010-05-11 | no assertion criteria provided | curation | Converted during submission to Pathogenic. |
| Leiden Muscular Dystrophy |
RCV000119545 | SCV000154452 | not provided | not provided | no assertion provided | not provided | ||
| OMIM | RCV000056236 | SCV005046822 | pathogenic | Central core myopathy | 2003-12-01 | no assertion criteria provided | literature only |