Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001556829 | SCV001778478 | uncertain significance | not provided | 2020-02-01 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Labcorp Genetics |
RCV001882641 | SCV002126847 | uncertain significance | RYR1-related disorder | 2022-07-14 | 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 1622 of the RYR1 protein (p.Arg1622Trp). 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: 1194181). 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. 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. |
| Revvity Omics, |
RCV001556829 | SCV003813083 | uncertain significance | not provided | 2019-08-01 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004039314 | SCV004945836 | uncertain significance | Inborn genetic diseases | 2024-01-17 | criteria provided, single submitter | clinical testing | The c.4864C>T (p.R1622W) alteration is located in exon 33 (coding exon 33) of the RYR1 gene. This alteration results from a C to T substitution at nucleotide position 4864, causing the arginine (R) at amino acid position 1622 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |