NM_004004.6(GJB2):c.598G>A (p.Gly200Arg) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 8, 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:: RCV001853379.6

Allele description [Variation Report for NM_004004.6(GJB2):c.598G>A (p.Gly200Arg)]

NM_004004.6(GJB2):c.598G>A (p.Gly200Arg)

Gene:

GJB2:gap junction protein beta 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

13q12.11

Genomic location:

Preferred name:

NM_004004.6(GJB2):c.598G>A (p.Gly200Arg)

HGVS:

NC_000013.11:g.20188984C>T
NG_008358.1:g.8992G>A
NM_004004.6:c.598G>AMANE SELECT
NP_003995.2:p.Gly200Arg
LRG_1350t1:c.598G>A
LRG_1350:g.8992G>A
LRG_1350p1:p.Gly200Arg
NC_000013.10:g.20763123C>T
NM_004004.5:c.598G>A

Protein change:

G200R

Links:

dbSNP: rs786204597

NCBI 1000 Genomes Browser:

rs786204597

Molecular consequence:

NM_004004.6:c.598G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002231530	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 8, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 23967136, 21094084, 24949729, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002231530

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 8, 2023)

germline

clinical testing

PubMed (4)
[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

Analysis of trafficking, stability and function of human connexin 26 gap junction channels with deafness-causing mutations in the fourth transmembrane helix.

Ambrosi C, Walker AE, Depriest AD, Cone AC, Lu C, Badger J, Skerrett IM, Sosinsky GE.

PLoS One. 2013;8(8):e70916. doi: 10.1371/journal.pone.0070916.

PubMed [citation]

PMID:: 23967136
PMCID:: PMC3744544

Multiple effects of childhood deafness on cortical activity in children receiving bilateral cochlear implants simultaneously.

Gordon KA, Tanaka S, Wong DD, Stockley T, Ramsden JD, Brown T, Jewell S, Papsin BC.

Clin Neurophysiol. 2011 Apr;122(4):823-33. doi: 10.1016/j.clinph.2010.10.037. Epub 2010 Nov 19.

PubMed [citation]

PMID:: 21094084

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002231530.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 200 of the GJB2 protein (p.Gly200Arg). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects GJB2 function (PMID: 23967136). 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 GJB2 protein function. ClinVar contains an entry for this variant (Variation ID: 225222). This missense change has been observed in individuals with autosomal recessive deafness (PMID: 21094084, 24949729). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency).

#	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: Oct 26, 2024

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