NM_004004.6(GJB2):c.229T>C (p.Trp77Arg) AND Rare genetic deafness

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 23, 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:: RCV000211765.14

Allele description [Variation Report for NM_004004.6(GJB2):c.229T>C (p.Trp77Arg)]

NM_004004.6(GJB2):c.229T>C (p.Trp77Arg)

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.229T>C (p.Trp77Arg)

HGVS:

NC_000013.11:g.20189353A>G
NG_008358.1:g.8623T>C
NM_004004.6:c.229T>CMANE SELECT
NP_003995.2:p.Trp77Arg
NP_003995.2:p.Trp77Arg
LRG_1350t1:c.229T>C
LRG_1350:g.8623T>C
LRG_1350p1:p.Trp77Arg
NC_000013.10:g.20763492A>G
P29033:p.Trp77Arg
c.229T>C
c.229T>C (p.Trp77Arg)

Protein change:

W77R; TRP77ARG

Links:

UniProtKB: P29033#VAR_002141; OMIM: 121011.0004; dbSNP: rs104894397

NCBI 1000 Genomes Browser:

rs104894397

Molecular consequence:

NM_004004.6:c.229T>C - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

loss_of_function_variant [Sequence Ontology: SO:0002054]

Condition(s)

Name:: Rare genetic deafness
Identifiers:: MedGen: C5680250; Orphanet: 96210

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000061487	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 23, 2022)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 9328482, 15964725, 15967879, 11102979, 16380907, 10982180, 11935342, 22785241, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000061487

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jun 23, 2022)

germline

clinical testing

PubMed (9)
[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

Two different connexin 26 mutations in an inbred kindred segregating non-syndromic recessive deafness: implications for genetic studies in isolated populations.

Carrasquillo MM, Zlotogora J, Barges S, Chakravarti A.

Hum Mol Genet. 1997 Nov;6(12):2163-72.

PubMed [citation]

PMID:: 9328482

Prevalence of GJB2 mutations and the del(GJB6-D13S1830) in Argentinean non-syndromic deaf patients.

Dalamón V, Béhèran A, Diamante F, Pallares N, Diamante V, Elgoyhen AB.

Hear Res. 2005 Sep;207(1-2):43-9.

PubMed [citation]

PMID:: 15964725

See all PubMed Citations (9)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000061487.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

The p.Trp77Arg variant has been reported in many individuals with hearing loss and was absent from many controls (Carrasquillo 1997 PMID: 9328482, Dalamón 2005 PMID: 15964725, Marlin 2005 PMID: 15967879, Prasad 2000 PMID: 11102979, Rabionet 2000 PMID: 10982180, Shahin 2002 PMID: 11935342, Snoeckx 2005 PMID: 16380907). It was also found to segregate with hearing loss in one large kindred (Carrasquillo 1997 PMID: 9328482). In summary, this variant meets our criteria to be classified as pathogenic. ACMG criteria applied: PM3_VeryStrong, PP1_Strong, PP3, PM2_Supporting.

#	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: Nov 3, 2024

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