NM_001184880.2(PCDH19):c.2728G>T (p.Glu910Ter) AND Developmental and epileptic encephalopathy, 9

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Aug 9, 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:: RCV001885229.5

Allele description [Variation Report for NM_001184880.2(PCDH19):c.2728G>T (p.Glu910Ter)]

NM_001184880.2(PCDH19):c.2728G>T (p.Glu910Ter)

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.2728G>T (p.Glu910Ter)

HGVS:

NC_000023.11:g.100342023C>A
NG_021319.1:g.73251G>T
NM_001105243.2:c.2587G>T
NM_001184880.2:c.2728G>TMANE SELECT
NM_020766.3:c.2584G>T
NP_001098713.1:p.Glu863Ter
NP_001171809.1:p.Glu910Ter
NP_065817.2:p.Glu862Ter
LRG_843t1:c.2728G>T
LRG_843:g.73251G>T
LRG_843p1:p.Glu910Ter
NC_000023.10:g.99597021C>A
NM_001184880.1:c.2728G>T

Protein change:

E862*

Links:

dbSNP: rs2147485081

NCBI 1000 Genomes Browser:

rs2147485081

Molecular consequence:

NM_001105243.2:c.2587G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001184880.2:c.2728G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_020766.3:c.2584G>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

Recent activity

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peroxisomal ATPase PEX1 isoform X1 [Homo sapiens]
peroxisomal ATPase PEX1 isoform X1 [Homo sapiens]
gi|2462614767|ref|XP_054214375.1|

Protein
Taxonomy Links for Nucleotide (Select 27552844) (1)
Taxonomy
Related DataSets for GEO Profiles (Select 65206245) (1)
GEO DataSets
Night and day effects on pineal gland (Expt. B)
Night and day effects on pineal gland (Expt. B)
Accession: GDS3700

GEO DataSets
SMC6 DNA repair protein SMC6 [Saccharomyces cerevisiae S288C]
SMC6 DNA repair protein SMC6 [Saccharomyces cerevisiae S288C]
Gene ID:851099

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002038584	Stanford Center for Inherited Cardiovascular Disease, Stanford University	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	de novo	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002133136	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 9, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21053371, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002038584

Stanford Center for Inherited Cardiovascular Disease, Stanford University

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic

de novo

clinical testing

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

SCV002133136

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 9, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

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 (3)

Details of each submission

From Stanford Center for Inherited Cardiovascular Disease, Stanford University, SCV002038584.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Asian	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	de novo	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002133136.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1328937). This variant has not been reported in the literature in individuals affected with PCDH19-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu910*) 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

Last Updated: Sep 29, 2024

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