Submissions for variant NM_145239.3(PRRT2):c.718C>T (p.Arg240Ter)

dbSNP: rs387907126

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000431690	SCV000516081	pathogenic	not provided	2015-03-24	criteria provided, single submitter	clinical testing	The R240X nonsense variant in the PRRT2 gene has been reported previously in association with paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC), PKD with migraines without aura, and benign familial infantile seizures (BFIS) (Lee et al., 2012; Cloarec et al., 2012; Labate et al., 2013). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. We interpret this variant as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000817890	SCV000958475	pathogenic	Episodic kinesigenic dyskinesia	2023-01-18	criteria provided, single submitter	clinical testing	The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 31174). This premature translational stop signal has been observed in individuals with paroxysmal kinesigenic dyskinesia or benign familial infantile seizures (PMID: 22832103, 23077017, 23352743). It has also been observed to segregate with disease in related individuals. This sequence change creates a premature translational stop signal (p.Arg240*) in the PRRT2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PRRT2 are known to be pathogenic (PMID: 22623405, 22744660).
Mendelics	RCV002247392	SCV002518917	pathogenic	Episodic kinesigenic dyskinesia 1	2022-05-04	criteria provided, single submitter	clinical testing
MGZ Medical Genetics Center	RCV002288519	SCV002579241	pathogenic	Seizures, benign familial infantile, 2	2021-09-02	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000431690	SCV004701572	pathogenic	not provided	2024-01-01	criteria provided, single submitter	clinical testing	PRRT2: PVS1, PP1:Strong, PM2, PS4:Moderate
OMIM	RCV000024172	SCV000045463	pathogenic	Infantile convulsions and choreoathetosis	2012-01-26	no assertion criteria provided	literature only