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NM_004004.6(GJB2):c.428G>A (p.Arg143Gln)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
9 (Most recent: May 20, 2019)
Last evaluated:
Feb 16, 2017
Accession:
VCV000017017.4
Variation ID:
17017
Description:
single nucleotide variant
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NM_004004.6(GJB2):c.428G>A (p.Arg143Gln)

Allele ID
32056
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
13q12.11
Genomic location
13: 20189154 (GRCh38) GRCh38 UCSC
13: 20763293 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000013.10:g.20763293C>T
NC_000013.11:g.20189154C>T
NM_004004.6:c.428G>A NP_003995.2:p.Arg143Gln missense
... more HGVS
Protein change
R143Q
Other names
-
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA257677
UniProtKB: P29033#VAR_015940
OMIM: 121011.0017
dbSNP: rs104894401
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 4 criteria provided, multiple submitters, no conflicts Jan 28, 2016 RCV000018542.27
Pathogenic/Likely pathogenic 3 criteria provided, multiple submitters, no conflicts Nov 3, 2016 RCV000018543.31
Pathogenic 2 criteria provided, multiple submitters, no conflicts Feb 16, 2017 RCV000484997.3
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
GJB2 Dosage sensitivity unlikely No evidence available GRCh38
GRCh37
296 345

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Nov 03, 2016)
criteria provided, single submitter
Method: clinical testing
Deafness, autosomal recessive 1A
Allele origin: germline
Integrated Genetics/Laboratory Corporation of America
Accession: SCV000698258.1
Submitted: (Jan 25, 2018)
Evidence details
Publications
PubMed (8)
Comment:
Variant summary: The GJB2 c.428G>A (p.Arg143Gln) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a damaging outcome for this variant ... (more)
Pathogenic
(Feb 16, 2017)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000568706.3
Submitted: (Jan 29, 2019)
Evidence details
Comment:
The c.428 G>A (p.R143Q) variant in the GJB2 gene has been reported previously in the compound heterozygous state in multiple unrelated individuals with congenital, profound, ... (more)
Likely pathogenic
(Jan 28, 2016)
criteria provided, single submitter
Method: clinical testing
Deafness, autosomal recessive 1A
Allele origin: unknown
Counsyl
Accession: SCV000487494.1
Submitted: (Nov 23, 2016)
Evidence details
Publications
PubMed (12)
Likely pathogenic
(Jan 28, 2016)
criteria provided, single submitter
Method: clinical testing
Deafness, autosomal dominant 3a
Allele origin: unknown
Counsyl
Accession: SCV000487495.1
Submitted: (Nov 23, 2016)
Evidence details
Publications
PubMed (12)
Pathogenic
(Dec 08, 2016)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics
Accession: SCV000703678.2
Submitted: (Sep 19, 2018)
Evidence details
Other databases
http://www.egl-eurofins.com/em...
Likely pathogenic
(-)
criteria provided, single submitter
Method: research
Deafness, autosomal dominant 3a
Allele origin: germline
Baylor-Hopkins Center for Mendelian Genomics,Johns Hopkins University
Accession: SCV000924176.1
Submitted: (May 20, 2019)
Comment:
This variant was present (heterozygous) in 2 individuals in the family who have the condition. Another GJB variant NM_004004.6: c.368C>A was present in one but ... (more)
Evidence details
Pathogenic
(Mar 01, 2001)
no assertion criteria provided
Method: literature only
DEAFNESS, AUTOSOMAL DOMINANT 3A
Allele origin: germline
OMIM
Accession: SCV000038824.3
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (1)
Pathogenic
(Mar 01, 2001)
no assertion criteria provided
Method: literature only
DEAFNESS, AUTOSOMAL RECESSIVE 1A
Allele origin: germline
OMIM
Accession: SCV000038825.3
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (1)
Pathogenic
(Dec 22, 2016)
no assertion criteria provided
Method: literature only
Deafness, autosomal dominant 3a
Allele origin: germline
GeneReviews
Accession: SCV000574687.1
Submitted: (Dec 22, 2016)
Evidence details
Other databases
https://www.ncbi.nlm.nih.gov/b...

Citations for this variant

Title Author Journal Year Link
Nonsyndromic Hearing Loss and Deafness, DFNA3 Smith RJH - 2016 PMID: 20301708
Long-Term Cochlear Implant Outcomes in Children with GJB2 and SLC26A4 Mutations. Wu CM PloS one 2015 PMID: 26397989
Mutation spectrum and prevalence of BRCA1 and BRCA2 genes in patients with familial and early-onset breast/ovarian cancer from Tunisia. Riahi A Clinical genetics 2015 PMID: 24372583
Compound heterozygosity for dominant and recessive GJB2 mutations in a Tunisian family and association with successful cochlear implant outcome. Riahi Z International journal of pediatric otorhinolaryngology 2013 PMID: 23856378
Identification of a p.R143Q dominant mutation in the gap junction beta-2 gene in three Chinese patients with different hearing phenotypes. Huang S Acta oto-laryngologica 2013 PMID: 22991996
Dominant Cx26 mutants associated with hearing loss have dominant-negative effects on wild type Cx26. Zhang J Molecular and cellular neurosciences 2011 PMID: 21040787
Dominant connexin26 mutants associated with human hearing loss have trans-dominant effects on connexin30. Yum SW Neurobiology of disease 2010 PMID: 20096356
Mutation analysis of familial GJB2-related deafness in Iranian Azeri Turkish patients. Bonyadi M Genetic testing and molecular biomarkers 2009 PMID: 19715472
A multicenter study of the frequency and distribution of GJB2 and GJB6 mutations in a large North American cohort. Putcha GV Genetics in medicine : official journal of the American College of Medical Genetics 2007 PMID: 17666888
Molecular genetics study of deafness in Brazil: 8-year experience. de Oliveira CA American journal of medical genetics. Part A 2007 PMID: 17567887
High incidence of GJB2 mutations during screening of newborns for hearing loss in Austria. Ramsebner R Ear and hearing 2007 PMID: 17485979
Detection of mutations in genes associated with hearing loss using a microarray-based approach. Siemering K The Journal of molecular diagnostics : JMD 2006 PMID: 16931589
Progressive hearing loss, and recurrent sudden sensorineural hearing loss associated with GJB2 mutations--phenotypic spectrum and frequencies of GJB2 mutations in Austria. Janecke AR Human genetics 2002 PMID: 12189487
Assessment of denaturing high-performance liquid chromatography (DHPLC) in screening for mutations in connexin 26 (GJB2). Lin D Human mutation 2001 PMID: 11438992
Sensorineural hearing loss and the incidence of Cx26 mutations in Austria. Löffler J European journal of human genetics : EJHG 2001 PMID: 11313763
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=GJB2 - - - -
https://www.ncbi.nlm.nih.gov/books/NBK1536/ - - - -

Record last updated Nov 10, 2019