NM_001184880.2(PCDH19):c.437C>G (p.Thr146Arg) AND Developmental and epileptic encephalopathy, 9

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 27, 2020
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:: RCV001378123.7

Allele description [Variation Report for NM_001184880.2(PCDH19):c.437C>G (p.Thr146Arg)]

NM_001184880.2(PCDH19):c.437C>G (p.Thr146Arg)

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.437C>G (p.Thr146Arg)

Other names:

p.T146R:ACG>AGG

HGVS:

NC_000023.11:g.100408161G>C
NG_021319.1:g.7113C>G
NM_001105243.2:c.437C>G
NM_001184880.2:c.437C>GMANE SELECT
NM_020766.3:c.437C>G
NP_001098713.1:p.Thr146Arg
NP_001171809.1:p.Thr146Arg
NP_065817.2:p.Thr146Arg
LRG_843t1:c.437C>G
LRG_843:g.7113C>G
LRG_843p1:p.Thr146Arg
NC_000023.10:g.99663159G>C
NM_001105243.1:c.437C>G
NM_001184880.1:c.437C>G
Q8TAB3:p.Thr146Arg

Protein change:

T146R

Links:

UniProtKB: Q8TAB3#VAR_064842; dbSNP: rs796052799

NCBI 1000 Genomes Browser:

rs796052799

Molecular consequence:

NM_001105243.2:c.437C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001184880.2:c.437C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_020766.3:c.437C>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
SCV001575623	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (May 27, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21053371, 27787195, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001575623

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(May 27, 2020)

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

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

Structural determinants of adhesion by Protocadherin-19 and implications for its role in epilepsy.

Cooper SR, Jontes JD, Sotomayor M.

Elife. 2016 Oct 26;5. doi:pii: e18529. 10.7554/eLife.18529.

PubMed [citation]

PMID:: 27787195
PMCID:: PMC5115871

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001575623.4

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

Description

This variant has been observed in individual(s) with seizures (PMID: 21053371, Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 206313). This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with arginine at codon 146 of the PCDH19 protein (p.Thr146Arg). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and arginine. 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. This variant has been reported to affect PCDH19 protein function (PMID: 27787195).

#	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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