Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Prevention |
RCV001207857 | SCV000852315 | uncertain significance | RYR1-related disorder | 2023-12-14 | criteria provided, single submitter | clinical testing | The RYR1 c.12842G>A variant is predicted to result in the amino acid substitution p.Gly4281Glu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.11% of alleles in individuals of African descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| Labcorp Genetics |
RCV001207857 | SCV001379224 | uncertain significance | RYR1-related disorder | 2024-01-11 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 4281 of the RYR1 protein (p.Gly4281Glu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 590416). 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 not expected to disrupt RYR1 protein function with a negative predictive value of 95%. 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, |
RCV002485816 | SCV002787271 | 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 | 2021-07-23 | criteria provided, single submitter | clinical testing | |
| Revvity Omics, |
RCV000721291 | SCV003827499 | uncertain significance | not provided | 2019-09-30 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000721291 | SCV003840298 | uncertain significance | not provided | 2023-03-07 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |