Submissions for variant NM_001184880.2(PCDH19):c.2675+1G>T

dbSNP: rs2520722295

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn	RCV002463407	SCV002757834	likely pathogenic	Developmental and epileptic encephalopathy, 9	2020-11-06	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002463407	SCV004492295	pathogenic	Developmental and epileptic encephalopathy, 9	2022-12-15	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 4 of the PCDH19 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PCDH19 are known to be pathogenic (PMID: 21053371). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with clinical features of PCDH19-related conditions (PMID: 27179713; Invitae). ClinVar contains an entry for this variant (Variation ID: 1801346). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.