Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001238869 | SCV001411702 | uncertain significance | Epileptic encephalopathy | 2022-08-23 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1503 of the RYR3 protein (p.Met1503Ile). This variant is present in population databases (rs199964676, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with RYR3-related conditions. ClinVar contains an entry for this variant (Variation ID: 964613). 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: "Benign"; Align-GVGD: "Class C0"). 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 | RCV002563929 | SCV003528846 | uncertain significance | Inborn genetic diseases | 2022-03-16 | criteria provided, single submitter | clinical testing | The c.4509G>A (p.M1503I) alteration is located in exon 34 (coding exon 34) of the RYR3 gene. This alteration results from a G to A substitution at nucleotide position 4509, causing the methionine (M) at amino acid position 1503 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |