NM_001184880.2(PCDH19):c.1360_1361delinsAA (p.Ser454Asn) AND Developmental and epileptic encephalopathy, 9

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 15, 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:: RCV001887315.5

Allele description [Variation Report for NM_001184880.2(PCDH19):c.1360_1361delinsAA (p.Ser454Asn)]

NM_001184880.2(PCDH19):c.1360_1361delinsAA (p.Ser454Asn)

Gene:

PCDH19:protocadherin 19 [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

Xq22.1

Genomic location:

Preferred name:

NM_001184880.2(PCDH19):c.1360_1361delinsAA (p.Ser454Asn)

HGVS:

NC_000023.11:g.100407237_100407238delinsTT
NG_021319.1:g.8036_8037delinsAA
NM_001105243.2:c.1360_1361delinsAA
NM_001184880.2:c.1360_1361delinsAAMANE SELECT
NM_020766.3:c.1360_1361delinsAA
NP_001098713.1:p.Ser454Asn
NP_001171809.1:p.Ser454Asn
NP_065817.2:p.Ser454Asn
LRG_843t1:c.1360_1361delinsAA
LRG_843:g.8036_8037delinsAA
LRG_843p1:p.Ser454Asn
NC_000023.10:g.99662235_99662236delinsTT

Protein change:

S454N

Links:

dbSNP: rs2147538982

NCBI 1000 Genomes Browser:

rs2147538982

Molecular consequence:

NM_001105243.2:c.1360_1361delinsAA - missense variant - [Sequence Ontology: SO:0001583]
NM_001184880.2:c.1360_1361delinsAA - missense variant - [Sequence Ontology: SO:0001583]
NM_020766.3:c.1360_1361delinsAA - 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
SCV002162808	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 15, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002162808

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 15, 2020)

germline

clinical testing

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

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

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002162808.2

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available"). This variant has not been reported in the literature in individuals with PCDH19-related conditions. The frequency data for this variant in the population databases is not available, as this variant may be reported as separate entries in the ExAC database. This sequence change replaces serine with asparagine at codon 454 of the PCDH19 protein (p.Ser454Asn). The serine residue is highly conserved and there is a small physicochemical difference between serine and asparagine.

#	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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