Submissions for variant NM_001184880.2(PCDH19):c.1133C>G (p.Ser378Ter)

dbSNP: rs1555985301

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics Inc	RCV000517162	SCV000614412	pathogenic	not provided	2017-03-30	criteria provided, single submitter	clinical testing
GeneDx	RCV000517162	SCV000890637	pathogenic	not provided	2018-09-27	criteria provided, single submitter	clinical testing	The S378X nonsense variant in the PCDH19 gene is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The S378X variant is not observed in large population cohorts (Lek et al., 2016). Although this pathogenic variant has not been reported previously to our knowledge, its presence is consistent with the diagnosis of a PCDH19-related disorder in this individual.
Invitae	RCV001064734	SCV001229652	pathogenic	Developmental and epileptic encephalopathy, 9	2022-12-06	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 447916). This premature translational stop signal has been observed in individual(s) with clinical features of early infantile epileptic encephalopathy (PMID: 30287595). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser378*) in the PCDH19 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PCDH19 are known to be pathogenic (PMID: 21053371).
Laboratory of Inherited Metabolic Diseases, Research centre for medical genetics	RCV001064734	SCV001245209	pathogenic	Developmental and epileptic encephalopathy, 9	2020-02-14	criteria provided, single submitter	clinical testing