Submissions for variant NM_001184880.2(PCDH19):c.1091dup (p.Tyr366fs)

dbSNP: rs758946412

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000188390	SCV000224336	pathogenic	not provided	2015-05-29	criteria provided, single submitter	clinical testing
GeneDx	RCV000188390	SCV000242002	pathogenic	not provided	2023-10-11	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Also known as c.1091_1092insC; This variant is associated with the following publications: (PMID: 23871722, 22050978, 27527380, 29056246, 27143072, 29301106, 29377098, 30451291, 31714027, 33262389, 33149276, 34177756, 18469813)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000173240	SCV000548732	pathogenic	Developmental and epileptic encephalopathy, 9	2024-12-02	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Tyr366Leufs*10) 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). 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. This premature translational stop signal has been observed in individual(s) with epilepsy and intellectual disability (PMID: 18469813, 22267240, 22946748, 23334464, 27143072, 27527380). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 206353). For these reasons, this variant has been classified as Pathogenic.
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000626781	SCV000747484	pathogenic	Global developmental delay; Long palpebral fissure; Delayed speech and language development; Strabismus; Prominent fingertip pads; Bilateral tonic-clonic seizure; Generalized non-motor (absence) seizure; Generalized-onset seizure; Hand tremor; Frontal cortical atrophy; Temporal cortical atrophy	2017-01-01	criteria provided, single submitter	clinical testing
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000173240	SCV000782225	pathogenic	Developmental and epileptic encephalopathy, 9	2016-11-01	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000188390	SCV001249611	pathogenic	not provided	2019-08-01	criteria provided, single submitter	clinical testing
Mendelics	RCV000173240	SCV002517857	pathogenic	Developmental and epileptic encephalopathy, 9	2022-05-04	criteria provided, single submitter	clinical testing
OMIM	RCV000173240	SCV000031994	pathogenic	Developmental and epileptic encephalopathy, 9	2008-06-01	no assertion criteria provided	literature only