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NM_001184880.2(PCDH19):c.619C>T (p.Arg207Ter) AND Developmental and epileptic encephalopathy, 9

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 16, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002272165.4

Allele description [Variation Report for NM_001184880.2(PCDH19):c.619C>T (p.Arg207Ter)]

NM_001184880.2(PCDH19):c.619C>T (p.Arg207Ter)

Gene:
PCDH19:protocadherin 19 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq22.1
Genomic location:
Preferred name:
NM_001184880.2(PCDH19):c.619C>T (p.Arg207Ter)
Other names:
p.R207*:CGA>TGA
HGVS:
  • NC_000023.11:g.100407979G>A
  • NG_021319.1:g.7295C>T
  • NM_001105243.2:c.619C>T
  • NM_001184880.2:c.619C>TMANE SELECT
  • NM_020766.3:c.619C>T
  • NP_001098713.1:p.Arg207Ter
  • NP_001171809.1:p.Arg207Ter
  • NP_065817.2:p.Arg207Ter
  • LRG_843t1:c.619C>T
  • LRG_843:g.7295C>T
  • LRG_843p1:p.Arg207Ter
  • NC_000023.10:g.99662977G>A
  • NM_001105243.1:c.619C>T
  • NM_001184880.1:c.619C>T
Protein change:
R207*
Links:
dbSNP: rs796052802
NCBI 1000 Genomes Browser:
rs796052802
Molecular consequence:
  • NM_001105243.2:c.619C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001184880.2:c.619C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_020766.3:c.619C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Developmental and epileptic encephalopathy, 9 (DEE9)
Synonyms:
EPILEPSY, FEMALE-RESTRICTED, WITH MENTAL RETARDATION; JUBERG-HELLMAN SYNDROME; PCDH19-Related X-Linked Female-Limited Epilepsy with Mental Retardation; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010246; MedGen: C1848137; Orphanet: 2076; OMIM: 300088

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002557507Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Jul 16, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Male patients affected by mosaic PCDH19 mutations: five new cases.

de Lange IM, Rump P, Neuteboom RF, Augustijn PB, Hodges K, Kistemaker AI, Brouwer OF, Mancini GMS, Newman HA, Vos YJ, Helbig KL, Peeters-Scholte C, Kriek M, Knoers NV, Lindhout D, Koeleman BPC, van Kempen MJA, Brilstra EH.

Neurogenetics. 2017 Jul;18(3):147-153. doi: 10.1007/s10048-017-0517-5. Epub 2017 Jul 1.

PubMed [citation]
PMID:
28669061
PMCID:
PMC5522515

PCDH19-related epilepsy is associated with a broad neurodevelopmental spectrum.

Smith L, Singhal N, El Achkar CM, Truglio G, Rosen Sheidley B, Sullivan J, Poduri A.

Epilepsia. 2018 Mar;59(3):679-689. doi: 10.1111/epi.14003. Epub 2018 Jan 28. Erratum in: Epilepsia. 2018 Jun;59(6):1272. doi: 10.1111/epi.14200.

PubMed [citation]
PMID:
29377098
PMCID:
PMC6264912
See all PubMed Citations (4)

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002557507.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with developmental and epileptic encephalopathy 9 (MIM#300088). (I) 0110 - This gene is associated with X-linked disease. Heterozygous females and mosaic males are affected, however hemizygous males do not present with symptoms (PMID: 28669061). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other NMD predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (DECIPHER). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been observed as a de novo event in two individuals with seizures (ClinVar, PMIDs: 29655203, 29377098). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1204 - This variant has been shown to be de novo in the proband (parental status not tested but assumed) (by segregation analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 29, 2024