NM_001184880.2(PCDH19):c.1178C>T (p.Pro393Leu) AND Developmental and epileptic encephalopathy, 9

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

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 14, 2022
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:: RCV003509062.1

Allele description

NM_001184880.2(PCDH19):c.1178C>T (p.Pro393Leu)

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.1178C>T (p.Pro393Leu)

HGVS:

NC_000023.11:g.100407420G>A
NG_021319.1:g.7854C>T
NM_001105243.2:c.1178C>T
NM_001184880.2:c.1178C>TMANE SELECT
NM_020766.3:c.1178C>T
NP_001098713.1:p.Pro393Leu
NP_001171809.1:p.Pro393Leu
NP_065817.2:p.Pro393Leu
LRG_843t1:c.1178C>T
LRG_843:g.7854C>T
LRG_843p1:p.Pro393Leu
NC_000023.10:g.99662418G>A

Protein change:

P393L

Molecular consequence:

NM_001105243.2:c.1178C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001184880.2:c.1178C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_020766.3:c.1178C>T - 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

Recent activity

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PREDICTED: Cucumis melo ATP synthase subunit epsilon, mitochondrial (LOC10350063...
PREDICTED: Cucumis melo ATP synthase subunit epsilon, mitochondrial (LOC103500632), mRNA
gi|2316531988|ref|XM_008464003.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004300140	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Nov 14, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25499160, 30287595, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004300140

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Nov 14, 2022)

germline

clinical testing

PubMed (3)
[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

Cognitive development in females with PCDH19 gene-related epilepsy.

Cappelletti S, Specchio N, Moavero R, Terracciano A, Trivisano M, Pontrelli G, Gentile S, Vigevano F, Cusmai R.

Epilepsy Behav. 2015 Jan;42:36-40. doi: 10.1016/j.yebeh.2014.10.019. Epub 2014 Dec 11.

PubMed [citation]

PMID:: 25499160

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

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV004300140.1

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

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PCDH19 protein function. This missense change has been observed in individual(s) with PCDH19-related epilepsy (PMID: 25499160, 30287595). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 393 of the PCDH19 protein (p.Pro393Leu).

#	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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