NM_001184880.2(PCDH19):c.1538del (p.Gly513fs) AND Developmental and epileptic encephalopathy, 9

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 26, 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:: RCV003623391.1

Allele description [Variation Report for NM_001184880.2(PCDH19):c.1538del (p.Gly513fs)]

NM_001184880.2(PCDH19):c.1538del (p.Gly513fs)

Gene:

PCDH19:protocadherin 19 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

Xq22.1

Genomic location:

Preferred name:

NM_001184880.2(PCDH19):c.1538del (p.Gly513fs)

HGVS:

NC_000023.11:g.100407061del
NG_021319.1:g.8214del
NM_001105243.2:c.1538del
NM_001184880.2:c.1538delMANE SELECT
NM_020766.3:c.1538del
NP_001098713.1:p.Gly513fs
NP_001171809.1:p.Gly513fs
NP_065817.2:p.Gly513fs
LRG_843t1:c.1538del
LRG_843:g.8214del
LRG_843p1:p.Gly513fs
NC_000023.10:g.99662058del
NC_000023.10:g.99662059del

Protein change:

G513fs

Molecular consequence:

NM_001105243.2:c.1538del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001184880.2:c.1538del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_020766.3:c.1538del - frameshift variant - [Sequence Ontology: SO:0001589]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004458709	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 26, 2023)	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

SCV004458709

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 26, 2023)

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

Citations

PubMed

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV004458709.1

#	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. 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.Gly513Alafs*56) 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: Feb 28, 2024

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