U.S. flag

An official website of the United States government

NM_001184880.2(PCDH19):c.3157C>T (p.Arg1053Trp) AND Developmental and epileptic encephalopathy, 9

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 10, 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:
RCV001216154.13

Allele description [Variation Report for NM_001184880.2(PCDH19):c.3157C>T (p.Arg1053Trp)]

NM_001184880.2(PCDH19):c.3157C>T (p.Arg1053Trp)

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.3157C>T (p.Arg1053Trp)
HGVS:
  • NC_000023.11:g.100296567G>A
  • NG_021319.1:g.118707C>T
  • NM_001105243.2:c.3016C>T
  • NM_001184880.2:c.3157C>TMANE SELECT
  • NM_020766.3:c.3013C>T
  • NP_001098713.1:p.Arg1006Trp
  • NP_001171809.1:p.Arg1053Trp
  • NP_065817.2:p.Arg1005Trp
  • LRG_843t1:c.3157C>T
  • LRG_843:g.118707C>T
  • LRG_843p1:p.Arg1053Trp
  • NC_000023.10:g.99551565G>A
  • NM_001184880.1:c.3157C>T
Protein change:
R1005W
Links:
dbSNP: rs774986147
NCBI 1000 Genomes Browser:
rs774986147
Molecular consequence:
  • NM_001105243.2:c.3016C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001184880.2:c.3157C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020766.3:c.3013C>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

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001387933Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Aug 10, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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, SCV001387933.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1053 of the PCDH19 protein (p.Arg1053Trp). This variant is present in population databases (rs774986147, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with PCDH19-related conditions. ClinVar contains an entry for this variant (Variation ID: 589955). 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 not expected to disrupt PCDH19 protein function. 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 3, 2024