Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001719806 | SCV000242395 | likely benign | not provided | 2021-03-27 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 20301633, 25502464, 23190448, 26598493, 31124310, 31154286) |
| Invitae | RCV000791448 | SCV000820972 | uncertain significance | Episodic kinesigenic dyskinesia | 2024-01-17 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 216 of the PRRT2 protein (p.Pro216Arg). This variant is present in population databases (rs76335820, gnomAD 0.03%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with PRRT2-related conditions (PMID: 23190448). ClinVar contains an entry for this variant (Variation ID: 65757). 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 does not substantially affect PRRT2 function (PMID: 31124310). 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. |
| Mendelics | RCV000055990 | SCV001140085 | likely benign | Episodic kinesigenic dyskinesia 1 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV001332952 | SCV001525398 | uncertain significance | Infantile convulsions and choreoathetosis | 2019-03-01 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Ambry Genetics | RCV002354247 | SCV002656047 | uncertain significance | Inborn genetic diseases | 2018-09-16 | criteria provided, single submitter | clinical testing | The p.P216R variant (also known as c.647C>G), located in coding exon 1 of the PRRT2 gene, results from a C to G substitution at nucleotide position 647. The proline at codon 216 is replaced by arginine, an amino acid with dissimilar properties. In one study, this alteration was detected as compound heterozygous with PRRT2 c.510dupT (p.Leu171Serfs3) in an individual with classic infantile convulsions and choreoathetosis (ICCA) and paroxysmal-kinesigenic-dyskinesia (PKD). Each parent carried one alteration and both were asymptomatic (Liu XR et al. Genes Brain Behav., 2013 Mar;12:234-40). Additionally, this alteration was listed as a polymorphism in one study summarizing PRRT2 alterations (Ebrahimi-Fakhari D et al. Brain, 2015 Dec;138:3476-95). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Gene |
RCV000055990 | SCV000087044 | not provided | Episodic kinesigenic dyskinesia 1 | no assertion provided | literature only |