ClinVar Miner

Submissions for variant NM_145239.3(PRRT2):c.593_594del (p.Pro198fs) (rs1260966131)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001009279 SCV001169101 likely pathogenic not provided 2019-02-26 criteria provided, single submitter clinical testing The c.593_594delCT variant has been reported previously in an individual with infantile convulsions with paroxysmal choreoathetosis syndrome and speech delay who inherited c.593_594delCT from her asymptomatic mother and also had another PRRT2 pathogenic variant that was inherited from her father with PKD (Zeng et al., 2018). The deletion causes a frameshift starting with codon Proline 198, changes this amino acid to a Arginine residue and creates a premature Stop codon at position 26 of the new reading frame, denoted p.Pro198ArgfsX26. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Furthermore, the c.593_594delCT variant is not observed in large population cohorts (Lek et al., 2016). Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Invitae RCV001389771 SCV001591224 pathogenic Paroxysmal kinesigenic dyskinesia 2020-10-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Pro198Argfs*26) in the PRRT2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with benign familial neonatal-infantile seizures (PMID: 29215089). ClinVar contains an entry for this variant (Variation ID: 818036). Loss-of-function variants in PRRT2 are known to be pathogenic (PMID: 22623405, 22744660). For these reasons, this variant has been classified as Pathogenic.

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