Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000278875 | SCV000341098 | uncertain significance | not provided | 2016-05-18 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001071016 | SCV001236297 | uncertain significance | RYR1-related disorder | 2022-09-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1016 of the RYR1 protein (p.Arg1016Gln). This variant is present in population databases (rs373541911, gnomAD 0.01%). 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: 287350). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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, |
RCV002494869 | SCV002775656 | 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 | 2021-09-09 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000278875 | SCV004236628 | uncertain significance | not provided | 2023-03-01 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV003995779 | SCV004817942 | uncertain significance | Malignant hyperthermia, susceptibility to, 1 | 2024-02-05 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with glutamine at codon 1016 of the RYR1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 11/278626 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. |