Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001352471 | SCV001547024 | uncertain significance | Epileptic encephalopathy | 2020-03-26 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with RYR3-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with isoleucine at codon 1159 of the RYR3 protein (p.Met1159Ile). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and isoleucine. |
| Ambry Genetics | RCV002547558 | SCV003707544 | uncertain significance | Inborn genetic diseases | 2022-01-05 | criteria provided, single submitter | clinical testing | The c.3477G>A (p.M1159I) alteration is located in exon 27 (coding exon 27) of the RYR3 gene. This alteration results from a G to A substitution at nucleotide position 3477, causing the methionine (M) at amino acid position 1159 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |