Submissions for variant NM_145239.3(PRRT2):c.871G>A (p.Ala291Thr)

dbSNP: rs1596893141

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000792681	SCV000931991	uncertain significance	Episodic kinesigenic dyskinesia	2023-02-26	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 291 of the PRRT2 protein (p.Ala291Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with paroxysmal kinesigenic dyskinesia (Invitae). ClinVar contains an entry for this variant (Variation ID: 639782). 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. This variant disrupts the p.Ala291 amino acid residue in PRRT2. Other variant(s) that disrupt this residue have been observed in individuals with PRRT2-related conditions (PMID: 23190448), which suggests that this may be a clinically significant amino acid residue. 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.
GeneDx	RCV003317369	SCV004021557	uncertain significance	not provided	2023-07-20	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge