Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000690827 | SCV000818555 | likely pathogenic | Episodic kinesigenic dyskinesia | 2024-01-17 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 295 of the PRRT2 protein (p.Arg295Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of PRRT2-related conditions (PMID: 23299620; Invitae). ClinVar contains an entry for this variant (Variation ID: 570056). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PRRT2 protein function. Experimental studies have shown that this missense change affects PRRT2 function (PMID: 30980674). This variant disrupts the p.Arg295 amino acid residue in PRRT2. Other variant(s) that disrupt this residue have been observed in individuals with PRRT2-related conditions (PMID: 23299620, 30392205, 31901402), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Gene |
RCV001756178 | SCV001985140 | uncertain significance | not provided | 2020-04-23 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; No data available from control populations to assess the frequency of this variant; Published functional studies demonstrate that R295Q exhibits reduced protein expression levels and mislocalization compared to wild-type but the degree of impact was not reliably replicated from one experiment to another (Tsai et al., 2019; Zhao et al., 2019); This variant is associated with the following publications: (PMID: 31124310, 30980674, 23299620, 26598494) |
| Revvity Omics, |
RCV001756178 | SCV004238603 | likely pathogenic | not provided | 2023-06-19 | criteria provided, single submitter | clinical testing |