NM_001184880.2(PCDH19):c.1526A>G (p.Asn509Ser) AND Developmental and epileptic encephalopathy, 9

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 15, 2021
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:: RCV001321821.6

Allele description

NM_001184880.2(PCDH19):c.1526A>G (p.Asn509Ser)

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.1526A>G (p.Asn509Ser)

HGVS:

NC_000023.11:g.100407072T>C
NG_021319.1:g.8202A>G
NM_001105243.2:c.1526A>G
NM_001184880.2:c.1526A>GMANE SELECT
NM_020766.3:c.1526A>G
NP_001098713.1:p.Asn509Ser
NP_001171809.1:p.Asn509Ser
NP_065817.2:p.Asn509Ser
LRG_843t1:c.1526A>G
LRG_843:g.8202A>G
LRG_843p1:p.Asn509Ser
NC_000023.10:g.99662070T>C
NM_001184880.1:c.1526A>G

Protein change:

N509S

Links:

dbSNP: rs1928381502

NCBI 1000 Genomes Browser:

rs1928381502

Molecular consequence:

NM_001105243.2:c.1526A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001184880.2:c.1526A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_020766.3:c.1526A>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001512670	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 15, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26704558, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001512670

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 15, 2021)

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

Exome-based analysis of cardiac arrhythmia, respiratory control, and epilepsy genes in sudden unexpected death in epilepsy.

Bagnall RD, Crompton DE, Petrovski S, Lam L, Cutmore C, Garry SI, Sadleir LG, Dibbens LM, Cairns A, Kivity S, Afawi Z, Regan BM, Duflou J, Berkovic SF, Scheffer IE, Semsarian C.

Ann Neurol. 2016 Apr;79(4):522-34. doi: 10.1002/ana.24596. Epub 2016 Feb 2.

PubMed [citation]

PMID:: 26704558

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, SCV001512670.4

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

Description

This variant has been observed in individual(s) with juvenile myoclonic epilepsy (PMID: 26704558). This sequence change replaces asparagine with serine at codon 509 of the PCDH19 protein (p.Asn509Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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 20, 2024

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