Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001303040 | SCV001492273 | uncertain significance | Episodic kinesigenic dyskinesia | 2021-03-03 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with PRRT2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with glycine at codon 217 of the PRRT2 protein (p.Arg217Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. |
| Ambry Genetics | RCV002539515 | SCV003559736 | uncertain significance | Inborn genetic diseases | 2021-07-19 | criteria provided, single submitter | clinical testing | The c.649C>G (p.R217G) alteration is located in exon 2 (coding exon 1) of the PRRT2 gene. This alteration results from a C to G substitution at nucleotide position 649, causing the arginine (R) at amino acid position 217 to be replaced by a glycine (G). Based on data from the Genome Aggregation Database (gnomAD), the PRRT2 c.649C>G alteration was not observed, with coverage at this position. This amino acid position is well conserved in available vertebrate species. The p.R217G alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |