Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000519798 | SCV000617308 | likely pathogenic | not provided | 2017-11-01 | criteria provided, single submitter | clinical testing | The R308C variant in the PRRT2 gene has been reported previously in individuals with paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) and sporadic PKD (Li et al., 2012; Lee et al., 2012b). The R308C variant is not observed in large population cohorts (Lek et al., 2016). The R308C 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. This substitution occurs at a position that is conserved across species. Functional analysis of the R308C variant indicates that it leads to reduced protein expression (Liu et al., 2016). We interpret R308C as a likely pathogenic variant. |
Invitae | RCV000644948 | SCV000766674 | uncertain significance | Episodic kinesigenic dyskinesia | 2021-03-30 | criteria provided, single submitter | clinical testing | This variant has been reported in the literature in individuals affected with paroxysmal kinesigenic dyskinesia (PMID: 22131361, 22870186). ClinVar contains an entry for this variant (Variation ID: 449322). 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. This variant has been reported to affect PRRT2 protein function (PMID: 27172900, 31124310). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with cysteine at codon 308 of the PRRT2 protein (p.Arg308Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. |
Mendelics | RCV002248752 | SCV002518922 | pathogenic | Episodic kinesigenic dyskinesia 1 | 2022-05-04 | criteria provided, single submitter | clinical testing | |
MGZ Medical Genetics Center | RCV002248752 | SCV002581097 | uncertain significance | Episodic kinesigenic dyskinesia 1 | 2022-08-03 | criteria provided, single submitter | clinical testing |