Variant summary: The c.341A>G (p.E114G) in GJB2 gene is a missense change that alters a non-conserved nucleotide and 4/5 in silico tools predict benign outcome. The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 1.5%, predominantly in individuals of East Asian descent (18,8%) including numerous homozygous occurrences. This frequency suggests that the variant is a common ethnic-specific functional polymorphism. The variant has been reported to be mainly found in complex form (in cis with V27I) and in trans with V27I ( as well as with other variants) in both affected and unaffected individuals. Ogawa et al., (2014) report this complex variant to be found in unaffected individual who also carried p.Y136X on the other allele. In several patients reported by Dai et al, this variant occurred as complex forms p.[E114G;V27I] and [E114G;V27I;R127H] in compound heterozygosity swith known pathogenic variants, such as c.35delG, c.235delC, c.299_300delAT,Y125X, and c.424_426delTTC. Of typical observation, two patients were compound heterozygous for this variant and c.235delC. Furthermore, the complex p.[E114G;V27I] also co-occurred in cis with a known pathogenic variant (V37I) in four patients suggesting this complex is not pathogenic. Several independent groups showed that E114 in isolation or in complex with V27I formed gap junctions comparable to controls. In the field, this variant is widely accepted to be a polymorphism (Shearer et al., 2014). Taken together, the variant was classified as Benign.
ClinVar Genomic variation as it relates to human health
NM_004004.6(GJB2):c.341A>G (p.Glu114Gly)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(21)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Benign/Likely benign
21
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
This variant is part of a Haplotype
- Identifiers
-
NM_004004.6(GJB2):c.341A>G (p.Glu114Gly)
Variation ID: 44739 Accession: VCV000044739.42
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 13q12.11 13: 20189241 (GRCh38) [ NCBI UCSC ] 13: 20763380 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Nov 23, 2014 Sep 29, 2024 Feb 1, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_004004.6:c.341A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003995.2:p.Glu114Gly missense NC_000013.11:g.20189241T>C NC_000013.10:g.20763380T>C NG_008358.1:g.8735A>G LRG_1350:g.8735A>G LRG_1350t1:c.341A>G LRG_1350p1:p.Glu114Gly P29033:p.Glu114Gly - Protein change
- E114G
- Other names
- -
- Canonical SPDI
- NC_000013.11:20189240:T:C
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
0.03095 (C)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00062
The Genome Aggregation Database (gnomAD) 0.00499
Trans-Omics for Precision Medicine (TOPMed) 0.01006
Exome Aggregation Consortium (ExAC) 0.01459
The Genome Aggregation Database (gnomAD), exomes 0.01495
1000 Genomes Project 30x 0.02858
1000 Genomes Project 0.03095
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| GJB2 | Dosage sensitivity unlikely | No evidence available |
GRCh38 GRCh37 |
570 | 637 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Benign (8) |
criteria provided, multiple submitters, no conflicts
|
Jun 27, 2016 | RCV000037838.41 | |
| Benign (4) |
criteria provided, multiple submitters, no conflicts
|
Jul 1, 2021 | RCV000505536.15 | |
| Benign (5) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2024 | RCV000588130.27 | |
| Benign (1) |
criteria provided, single submitter
|
Mar 6, 2018 | RCV001112560.12 | |
| Benign (2) |
criteria provided, multiple submitters, no conflicts
|
Jul 1, 2021 | RCV001112559.13 | |
| Likely benign (1) |
criteria provided, single submitter
|
May 9, 2022 | RCV002496602.8 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Benign
(Feb 08, 2013)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV000193168.1
First in ClinVar: Nov 23, 2014 Last updated: Nov 23, 2014 |
|
|
|
Benign
(Apr 13, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000698246.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
Comment:
Variant summary: The c.341A>G (p.E114G) in GJB2 gene is a missense change that alters a non-conserved nucleotide and 4/5 in silico tools predict benign outcome. … (more)
Variant summary: The c.341A>G (p.E114G) in GJB2 gene is a missense change that alters a non-conserved nucleotide and 4/5 in silico tools predict benign outcome. The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 1.5%, predominantly in individuals of East Asian descent (18,8%) including numerous homozygous occurrences. This frequency suggests that the variant is a common ethnic-specific functional polymorphism. The variant has been reported to be mainly found in complex form (in cis with V27I) and in trans with V27I ( as well as with other variants) in both affected and unaffected individuals. Ogawa et al., (2014) report this complex variant to be found in unaffected individual who also carried p.Y136X on the other allele. In several patients reported by Dai et al, this variant occurred as complex forms p.[E114G;V27I] and [E114G;V27I;R127H] in compound heterozygosity swith known pathogenic variants, such as c.35delG, c.235delC, c.299_300delAT,Y125X, and c.424_426delTTC. Of typical observation, two patients were compound heterozygous for this variant and c.235delC. Furthermore, the complex p.[E114G;V27I] also co-occurred in cis with a known pathogenic variant (V37I) in four patients suggesting this complex is not pathogenic. Several independent groups showed that E114 in isolation or in complex with V27I formed gap junctions comparable to controls. In the field, this variant is widely accepted to be a polymorphism (Shearer et al., 2014). Taken together, the variant was classified as Benign. (less)
|
|
|
Benign
(Jun 27, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000513147.4
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
|
|
|
Benign
(Nov 29, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Athena Diagnostics
Accession: SCV000841704.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
|
|
|
Benign
(Aug 14, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: not provided
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000061500.5
First in ClinVar: May 03, 2013 Last updated: Mar 08, 2017 |
Comment:
Glu114Gly in exon 2 of GJB2: This variant is not expected to have clinical signi ficance because it has been identified in 10-20% Asian chromosomes … (more)
Glu114Gly in exon 2 of GJB2: This variant is not expected to have clinical signi ficance because it has been identified in 10-20% Asian chromosomes by several st udies (http://www.1000genomes.org; dbSNP rs2274083; Park 2000, Choung 2002, Watt anasirichaigoon 2004, Tekin 2010, Tsukada 2010, Wei 2013). (less)
Number of individuals with the variant: 11
|
|
|
Likely benign
(May 09, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Mutilating keratoderma
Autosomal dominant keratitis-ichthyosis-hearing loss syndrome Palmoplantar keratoderma-deafness syndrome Knuckle pads, deafness AND leukonychia syndrome Autosomal recessive nonsyndromic hearing loss 1A X-linked mixed hearing loss with perilymphatic gusher Autosomal dominant nonsyndromic hearing loss 3A Ichthyosis, hystrix-like, with hearing loss
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002809664.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
|
Benign
(Jul 19, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000603814.8
First in ClinVar: Mar 08, 2017 Last updated: Feb 20, 2024 |
|
|
|
Benign
(-)
|
criteria provided, single submitter
Method: clinical testing
|
NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000309914.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
|
|
|
Benign
(May 09, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Deafness, autosomal recessive 1A
Affected status: yes
Allele origin:
germline
|
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia
Accession: SCV000599746.1
First in ClinVar: Sep 19, 2017 Last updated: Sep 19, 2017 |
Number of individuals with the variant: 11
|
|
|
Benign
(Nov 14, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000112267.8
First in ClinVar: Jan 17, 2014 Last updated: May 03, 2018 |
Number of individuals with the variant: 11
Sex: mixed
|
|
|
Benign
(Mar 06, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal recessive nonsyndromic hearing loss 1A
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000383014.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
|
|
|
Benign
(Mar 06, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Ichthyosis, hystrix-like, with hearing loss
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001270224.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
|
|
|
Benign
(Mar 06, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal dominant nonsyndromic hearing loss 3A
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001270223.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
|
|
|
Benign
(Jul 01, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal recessive nonsyndromic hearing loss 1A
Affected status: no
Allele origin:
germline
|
Pars Genome Lab
Accession: SCV001749994.1
First in ClinVar: Jul 18, 2021 Last updated: Jul 18, 2021 |
Sex: mixed
|
|
|
Benign
(Jul 01, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal dominant nonsyndromic hearing loss 3A
Affected status: no
Allele origin:
germline
|
Pars Genome Lab
Accession: SCV001749995.1
First in ClinVar: Jul 18, 2021 Last updated: Jul 18, 2021 |
Sex: mixed
|
|
|
Benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001721606.4
First in ClinVar: Jun 15, 2021 Last updated: Feb 20, 2024 |
|
|
|
Benign
(-)
|
criteria provided, single submitter
Method: not provided
|
not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005230751.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
|
|
|
Benign
(Sep 16, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Autosomal recessive deafness type 1A
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV001463376.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001743078.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001958482.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001974765.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021 |
|
|
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Comment:
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Comment:
Glu114Gly in exon 2 of GJB2: This variant is not expected to have clinical signi ficance because it has been identified in 10-20% Asian chromosomes by several st udies (http://www.1000genomes.org; dbSNP rs2274083; Park 2000, Choung 2002, Watt anasirichaigoon 2004, Tekin 2010, Tsukada 2010, Wei 2013).
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
Variant summary: The c.341A>G (p.E114G) in GJB2 gene is a missense change that alters a non-conserved nucleotide and 4/5 in silico tools predict benign outcome. The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 1.5%, predominantly in individuals of East Asian descent (18,8%) including numerous homozygous occurrences. This frequency suggests that the variant is a common ethnic-specific functional polymorphism. The variant has been reported to be mainly found in complex form (in cis with V27I) and in trans with V27I ( as well as with other variants) in both affected and unaffected individuals. Ogawa et al., (2014) report this complex variant to be found in unaffected individual who also carried p.Y136X on the other allele. In several patients reported by Dai et al, this variant occurred as complex forms p.[E114G;V27I] and [E114G;V27I;R127H] in compound heterozygosity swith known pathogenic variants, such as c.35delG, c.235delC, c.299_300delAT,Y125X, and c.424_426delTTC. Of typical observation, two patients were compound heterozygous for this variant and c.235delC. Furthermore, the complex p.[E114G;V27I] also co-occurred in cis with a known pathogenic variant (V37I) in four patients suggesting this complex is not pathogenic. Several independent groups showed that E114 in isolation or in complex with V27I formed gap junctions comparable to controls. In the field, this variant is widely accepted to be a polymorphism (Shearer et al., 2014). Taken together, the variant was classified as Benign.
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Comment:
Glu114Gly in exon 2 of GJB2: This variant is not expected to have clinical signi ficance because it has been identified in 10-20% Asian chromosomes by several st udies (http://www.1000genomes.org; dbSNP rs2274083; Park 2000, Choung 2002, Watt anasirichaigoon 2004, Tekin 2010, Tsukada 2010, Wei 2013).
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Long Term Speech Perception Outcomes of Cochlear Implantation in Gap Junction Protein Beta 2 Related Hearing Loss. | Kim SH | Journal of audiology & otology | 2017 | PMID: 28704896 |
| Concomitant imaging and genetic findings in children with unilateral sensorineural hearing loss. | Gruber M | The Journal of laryngology and otology | 2017 | PMID: 28651654 |
| Mutation analysis of common GJB2, SCL26A4 and 12S rRNA genes among 380 deafness patients in northern China. | Pan J | International journal of pediatric otorhinolaryngology | 2017 | PMID: 28583500 |
| Reassessment of Genomic Sequence Variation to Harmonize Interpretation for Personalized Medicine. | Garber KB | American journal of human genetics | 2016 | PMID: 27843123 |
| Prevalence of GJB2 gene mutation in 330 cochlear implant patients in the Jiangsu province. | Shi L | The Journal of laryngology and otology | 2016 | PMID: 27534436 |
| Evaluation of ACMG-Guideline-Based Variant Classification of Cancer Susceptibility and Non-Cancer-Associated Genes in Families Affected by Breast Cancer. | Maxwell KN | American journal of human genetics | 2016 | PMID: 27153395 |
| The homozygote p.V27I/p.E114G variant of GJB2 is a putative indicator of nonsyndromic hearing loss in Chinese infants. | Chen WX | International journal of pediatric otorhinolaryngology | 2016 | PMID: 27063752 |
| NGS-Based Assay for the Identification of Individuals Carrying Recessive Genetic Mutations in Reproductive Medicine. | Abulí A | Human mutation | 2016 | PMID: 26990548 |
| Prevalence and audiological profiles of GJB2 mutations in a large collective of hearing impaired patients. | Burke WF | Hearing research | 2016 | PMID: 26778469 |
| Prevalence of p.V37I variant of GJB2 among Chinese infants with mild or moderate hearing loss. | Huang Y | International journal of clinical and experimental medicine | 2015 | PMID: 26885124 |
| The Prevalence of Gap Junction Protein Beta 2 (GJB2) Mutations in Non Syndromic Sensorineural Hearing Loss in Çukurova Region. | Bozdoğan ST | The journal of international advanced otology | 2015 | PMID: 26381000 |
| A study of deafness-related genetic mutations as a basis for strategies to prevent hereditary hearing loss in Hebei, China. | Zhu J | Intractable & rare diseases research | 2015 | PMID: 26361564 |
| Cordblood-Based High-Throughput Screening for Deafness Gene of 646 Newborns in Jinan Area of China. | Li SX | Clinical and experimental otorhinolaryngology | 2015 | PMID: 26330914 |
| Mutation Spectrum of Common Deafness-Causing Genes in Patients with Non-Syndromic Deafness in the Xiamen Area, China. | Jiang Y | PloS one | 2015 | PMID: 26252218 |
| Spectrum and frequency of GJB2, GJB6 and SLC26A4 gene mutations among nonsyndromic hearing loss patients in eastern part of India. | Adhikary B | Gene | 2015 | PMID: 26188157 |
| Carrier frequency of the GJB2 mutations that cause hereditary hearing loss in the Japanese population. | Taniguchi M | Journal of human genetics | 2015 | PMID: 26178431 |
| Correlation analysis of phenotype and genotype of GJB2 in patients with non-syndromic hearing loss in China. | Dai ZY | Gene | 2015 | PMID: 26095810 |
| GJB2 Mutation Spectrum and Genotype-Phenotype Correlation in 1067 Han Chinese Subjects with Non-Syndromic Hearing Loss. | Zheng J | PloS one | 2015 | PMID: 26043044 |
| SNPscan as a high-performance screening tool for mutation hotspots of hearing loss-associated genes. | Li H | Genomics | 2015 | PMID: 26004784 |
| Bioinformatic Analysis of GJB2 Gene Missense Mutations. | Yilmaz A | Cell biochemistry and biophysics | 2015 | PMID: 25388846 |
| The promoter mutation c.-259C>T (-3438C>T) is not a common cause of non-syndromic hearing impairment in Austria. | Koenighofer M | European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery | 2015 | PMID: 25085637 |
| Utilizing ethnic-specific differences in minor allele frequency to recategorize reported pathogenic deafness variants. | Shearer AE | American journal of human genetics | 2014 | PMID: 25262649 |
| Revertant mutation releases confined lethal mutation, opening Pandora's box: a novel genetic pathogenesis. | Ogawa Y | PLoS genetics | 2014 | PMID: 24785414 |
| Prevalence and range of GJB2 and SLC26A4 mutations in patients with autosomal recessive non‑syndromic hearing loss. | Jiang H | Molecular medicine reports | 2014 | PMID: 24737404 |
| Update of the spectrum of GJB2 mutations in 107 patients with nonsyndromic hearing loss in the Fujian population of China. | Chen T | Annals of human genetics | 2014 | PMID: 24645897 |
| Spectrum and frequency of GJB2 mutations causing deafness in the northwest of Iran. | Bonyadi MJ | International journal of pediatric otorhinolaryngology | 2014 | PMID: 24529908 |
| Prevalence of GJB2 mutations in the Silk Road region of China and a report of three novel variants. | Du W | Acta oto-laryngologica | 2014 | PMID: 24256046 |
| Genetic mutations of GJB2 and mitochondrial 12S rRNA in nonsyndromic hearing loss in Jiangsu Province of China. | Wei Q | Journal of translational medicine | 2013 | PMID: 23826813 |
| Does congenital cytomegalovirus infection lead to hearing loss by inducing mutation of the GJB2 gene? | Li LQ | Pediatric research | 2013 | PMID: 23665763 |
| Novel mutations of SLC26A4 in Chinese patients with nonsyndromic hearing loss. | Yao G | Acta oto-laryngologica | 2013 | PMID: 23638949 |
| Etiology and audiological outcomes at 3 years for 364 children in Australia. | Dahl HH | PloS one | 2013 | PMID: 23555729 |
| Congenital cholesteatoma and cochlear implantation: Implications for management. | Chung J | Cochlear implants international | 2013 | PMID: 22450542 |
| Mutation detection in GJB2 gene among Malays with non-syndromic hearing loss. | Zainal SA | International journal of pediatric otorhinolaryngology | 2012 | PMID: 22613756 |
| Allelic discrimination of cis-trans relationships by digital polymerase chain reaction: GJB2 (p.V27I/p.E114G) and CFTR (p.R117H/5T). | Chen N | Genetics in medicine : official journal of the American College of Medical Genetics | 2011 | PMID: 21836520 |
| Functional evaluation of GJB2 variants in nonsyndromic hearing loss. | Choi SY | Molecular medicine (Cambridge, Mass.) | 2011 | PMID: 21298213 |
| Prevalence of GJB2-associated deafness and outcomes of cochlear implantation in Iran. | Daneshi A | The Journal of laryngology and otology | 2011 | PMID: 21281533 |
| Genotyping with a 198 mutation arrayed primer extension array for hereditary hearing loss: assessment of its diagnostic value for medical practice. | Rodriguez-Paris J | PloS one | 2010 | PMID: 20668687 |
| Sequence Variations and Haplotypes of the GJB2 Gene Revealed by Resequencing of 192 Chromosomes from the General Population in Korea. | Kim HJ | Clinical and experimental otorhinolaryngology | 2010 | PMID: 20607074 |
| A large cohort study of GJB2 mutations in Japanese hearing loss patients. | Tsukada K | Clinical genetics | 2010 | PMID: 20497192 |
| GJB2 mutations in Mongolia: complex alleles, low frequency, and reduced fitness of the deaf. | Tekin M | Annals of human genetics | 2010 | PMID: 20201936 |
| Single nucleotide polymorphisms and haplotypes analysis of DFNB1 locus in Chinese sporadic hearing impairment population. | Cheng HB | Chinese medical journal | 2009 | PMID: 19719946 |
| High prevalence of the connexin 26 (GJB2) mutation in Chinese cochlear implant recipients. | Chen D | ORL; journal for oto-rhino-laryngology and its related specialties | 2009 | PMID: 19707039 |
| GJB2 mutation spectrum in 2,063 Chinese patients with nonsyndromic hearing impairment. | Dai P | Journal of translational medicine | 2009 | PMID: 19366456 |
| Congenital deafness: high prevalence of a V37I mutation in the GJB2 gene among deaf school children in Alor Setar. | Ruszymah BH | The Medical journal of Malaysia | 2005 | PMID: 16379178 |
| First molecular screening of deafness in the Altai Republic population. | Posukh O | BMC medical genetics | 2005 | PMID: 15790391 |
| GJB2 mutations: passage through Iran. | Najmabadi H | American journal of medical genetics. Part A | 2005 | PMID: 15666300 |
| GJB2 gene mutations in newborns with non-syndromic hearing impairment in Northern China. | Shi GZ | Hearing research | 2004 | PMID: 15504600 |
| High prevalence of V37I genetic variant in the connexin-26 (GJB2) gene among non-syndromic hearing-impaired and control Thai individuals. | Wattanasirichaigoon D | Clinical genetics | 2004 | PMID: 15479191 |
| Molecular epidemiology of DFNB1 deafness in France. | Roux AF | BMC medical genetics | 2004 | PMID: 15070423 |
| Evidence of a founder effect for the 235delC mutation of GJB2 (connexin 26) in east Asians. | Yan D | Human genetics | 2003 | PMID: 14505035 |
| Frequency and distribution of GJB2 (connexin 26) and GJB6 (connexin 30) mutations in a large North American repository of deaf probands. | Pandya A | Genetics in medicine : official journal of the American College of Medical Genetics | 2003 | PMID: 12865758 |
| Mutation spectrum of the connexin 26 (GJB2) gene in Taiwanese patients with prelingual deafness. | Hwa HL | Genetics in medicine : official journal of the American College of Medical Genetics | 2003 | PMID: 12792423 |
| Contribution of connexin26 (GJB2) mutations and founder effect to non-syndromic hearing loss in India. | RamShankar M | Journal of medical genetics | 2003 | PMID: 12746422 |
| Spectrum of GJB2 mutations in Turkey comprises both Caucasian and Oriental variants: roles of parental consanguinity and assortative mating. | Tekin M | Human mutation | 2003 | PMID: 12673800 |
| Functional study of GJB2 in hereditary hearing loss. | Choung YH | The Laryngoscope | 2002 | PMID: 12352684 |
| Effectiveness of sequencing connexin 26 (GJB2) in cases of familial or sporadic childhood deafness referred for molecular diagnostic testing. | Wu BL | Genetics in medicine : official journal of the American College of Medical Genetics | 2002 | PMID: 12172394 |
| GJB2 (connexin 26) variants and nonsyndromic sensorineural hearing loss: a HuGE review. | Kenneson A | Genetics in medicine : official journal of the American College of Medical Genetics | 2002 | PMID: 12172392 |
| GJB2 (connexin 26) mutations and childhood deafness in Thailand. | Kudo T | Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology | 2001 | PMID: 11698809 |
| Recurrent mutations in the deafness gene GJB2 (connexin 26) in British Asian families. | Rickard S | Journal of medical genetics | 2001 | PMID: 11494963 |
| Connexin 26 gene mutations in congenitally deaf children: pitfalls for genetic counseling. | Marlin S | Archives of otolaryngology--head & neck surgery | 2001 | PMID: 11493200 |
| Connexin26 mutations associated with nonsyndromic hearing loss. | Park HJ | The Laryngoscope | 2000 | PMID: 10983956 |
| Prevalent connexin 26 gene (GJB2) mutations in Japanese. | Abe S | Journal of medical genetics | 2000 | PMID: 10633133 |
| Novel mutations in the connexin 26 gene (GJB2) responsible for childhood deafness in the Japanese population. | Kudo T | American journal of medical genetics | 2000 | PMID: 10607953 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=GJB2 | - | - | - | - |
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Text-mined citations for rs2274083 ...
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Record last updated Nov 10, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.