Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000188773 | SCV000242397 | uncertain significance | not provided | 2019-01-07 | criteria provided, single submitter | clinical testing | p.Arg311Trp (R311W) CGG>TGG: c.931 C>T in exon 3 of the PRRT2 gene (NM_145239.2)The R311W variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R311W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In addition, this substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Some individuals with PRRT2 mutations never develop seizures due to incomplete penetrance. This variant has been observed to be maternally inherited from an apparently unaffected mother; The variant is found in EPILEPSY panel(s). |
Invitae | RCV001307468 | SCV001496882 | uncertain significance | Episodic kinesigenic dyskinesia | 2023-02-25 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 206691). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 311 of the PRRT2 protein (p.Arg311Trp). This variant is present in population databases (rs760521217, gnomAD 0.02%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with clinical features of PRRT2-related conditions (PMID: 26446061, 31130284). 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) performed at Invitae indicates that this missense variant is expected to disrupt PRRT2 protein function. Experimental studies have shown that this missense change does not substantially affect PRRT2 function (PMID: 30980674, 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. |
Equipe Genetique des Anomalies du Developpement, |
RCV001358685 | SCV001554494 | likely pathogenic | Seizures, benign familial infantile, 2 | criteria provided, single submitter | clinical testing |