Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001298476 | SCV001487534 | uncertain significance | Epileptic encephalopathy | 2020-03-06 | 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 isoleucine 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 (rs572913737, ExAC 0.2%). This sequence change replaces valine with isoleucine at codon 65 of the RYR3 protein (p.Val65Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine. |
| Ambry Genetics | RCV002543066 | SCV003590664 | uncertain significance | Inborn genetic diseases | 2021-08-12 | criteria provided, single submitter | clinical testing | The c.193G>A (p.V65I) alteration is located in exon 3 (coding exon 3) of the RYR3 gene. This alteration results from a G to A substitution at nucleotide position 193, causing the valine (V) at amino acid position 65 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |