Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001294818 | SCV001483713 | uncertain significance | Epileptic encephalopathy | 2020-05-11 | 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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 present in population databases (rs754630341, ExAC 0.002%). This sequence change replaces arginine with glutamine at codon 1078 of the RYR3 protein (p.Arg1078Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. |
| Ambry Genetics | RCV002538444 | SCV003532962 | uncertain significance | Inborn genetic diseases | 2022-04-21 | criteria provided, single submitter | clinical testing | The c.3233G>A (p.R1078Q) alteration is located in exon 26 (coding exon 26) of the RYR3 gene. This alteration results from a G to A substitution at nucleotide position 3233, causing the arginine (R) at amino acid position 1078 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |