Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001942758 | SCV002134808 | uncertain significance | RYR1-related disorder | 2021-07-04 | criteria provided, single submitter | clinical testing | 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"). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with lysine at codon 4837 of the RYR1 protein (p.Gln4837Lys). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and lysine. 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. |
| Ambry Genetics | RCV004953207 | SCV005496898 | uncertain significance | Inborn genetic diseases | 2024-08-12 | criteria provided, single submitter | clinical testing | The c.14509C>A (p.Q4837K) alteration is located in exon 100 (coding exon 100) of the RYR1 gene. This alteration results from a C to A substitution at nucleotide position 14509, causing the glutamine (Q) at amino acid position 4837 to be replaced by a lysine (K). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be deleterious by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |