NM_001184880.2(PCDH19):c.1133C>G (p.Ser378Ter) AND Developmental and epileptic encephalopathy, 9

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 6, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001064734.8

Allele description [Variation Report for NM_001184880.2(PCDH19):c.1133C>G (p.Ser378Ter)]

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

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.1133C>G (p.Ser378Ter)

HGVS:

NC_000023.11:g.100407465G>C
NG_021319.1:g.7809C>G
NM_001105243.2:c.1133C>G
NM_001184880.2:c.1133C>GMANE SELECT
NM_020766.3:c.1133C>G
NP_001098713.1:p.Ser378Ter
NP_001171809.1:p.Ser378Ter
NP_065817.2:p.Ser378Ter
LRG_843t1:c.1133C>G
LRG_843:g.7809C>G
LRG_843p1:p.Ser378Ter
NC_000023.10:g.99662463G>C
NM_001184880.1:c.1133C>G
p.Ser378*

Protein change:

S378*

Links:

dbSNP: rs1555985301

NCBI 1000 Genomes Browser:

rs1555985301

Molecular consequence:

NM_001105243.2:c.1133C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001184880.2:c.1133C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_020766.3:c.1133C>G - 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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MSV249 [Melanoplus sanguinipes entomopoxvirus]
MSV249 [Melanoplus sanguinipes entomopoxvirus]
Gene ID:1449988

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001229652	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 6, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 30287595, 21053371, 28492532
SCV001245209	Laboratory of Inherited Metabolic Diseases, Research centre for medical genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 14, 2020)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001229652

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 6, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV001245209

Laboratory of Inherited Metabolic Diseases, Research centre for medical genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 14, 2020)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mosaicism and incomplete penetrance of PCDH19 mutations.

Liu A, Yang X, Yang X, Wu Q, Zhang J, Sun D, Yang Z, Jiang Y, Wu X, Wei L, Zhang Y.

J Med Genet. 2019 Feb;56(2):81-88. doi: 10.1136/jmedgenet-2017-105235. Epub 2018 Oct 4.

PubMed [citation]

PMID:: 30287595
PMCID:: PMC6581080

Mutations and deletions in PCDH19 account for various familial or isolated epilepsies in females.

Depienne C, Trouillard O, Bouteiller D, Gourfinkel-An I, Poirier K, Rivier F, Berquin P, Nabbout R, Chaigne D, Steschenko D, Gautier A, Hoffman-Zacharska D, Lannuzel A, Lackmy-Port-Lis M, Maurey H, Dusser A, Bru M, Gilbert-Dussardier B, Roubertie A, Kaminska A, Whalen S, Mignot C, et al.

Hum Mutat. 2011 Jan;32(1):E1959-75. doi: 10.1002/humu.21373.

PubMed [citation]

PMID:: 21053371
PMCID:: PMC3033517

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001229652.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

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).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Laboratory of Inherited Metabolic Diseases, Research centre for medical genetics, SCV001245209.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 7, 2024

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