VCV000189183.23 - ClinVar

NM_004004.6(GJB2):c.596C>T (p.Ser199Phe)

Germline

Classification

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.

(11)

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.

Pathogenic/Likely pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_004004.6(GJB2):c.596C>T (p.Ser199Phe)

Variation ID: 189183 Accession: VCV000189183.23

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 13q12.11 13: 20188986 (GRCh38) [ NCBI UCSC ] 13: 20763125 (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	Mar 29, 2015	Feb 14, 2024	Jan 30, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_004004.6:c.596C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_003995.2:p.Ser199Phe	missense
NC_000013.11:g.20188986G>A
NC_000013.10:g.20763125G>A
NG_008358.1:g.8990C>T
LRG_1350:g.8990C>T
LRG_1350t1:c.596C>T	LRG_1350p1:p.Ser199Phe

... more HGVS ... less HGVS

Protein change

S199F

Other names

Canonical SPDI

NC_000013.11:20188985:G:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

Allele frequency Help The frequency of the allele represented by this VCV record.

Trans-Omics for Precision Medicine (TOPMed) 0.00000

Exome Aggregation Consortium (ExAC) 0.00001

The Genome Aggregation Database (gnomAD), exomes 0.00001

The Genome Aggregation Database (gnomAD) 0.00002

Links

ClinGen: CA274470 dbSNP: rs771748289 VarSome

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
Gene	OMIM	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.
Autosomal recessive nonsyndromic hearing loss 1A	Pathogenic/Likely pathogenic (2)	criteria provided, multiple submitters, no conflicts	Sep 11, 2017	RCV000169613.3
Rare genetic deafness	Pathogenic (1)	criteria provided, single submitter	Sep 15, 2016	RCV000609655.4
not provided	Pathogenic (6)	criteria provided, multiple submitters, no conflicts	Jan 30, 2024	RCV000991850.18
Autosomal dominant keratitis-ichthyosis-hearing loss syndrome Autosomal dominant nonsyndromic hearing loss 3A Autosomal recessive nonsyndromic hearing loss 1A Ichthyosis, hystrix-like, with hearing loss Knuckle pads, deafness AND leukonychia syndrome Mutilating keratoderma Palmoplantar keratoderma-deafness syndrome	Pathogenic (1)	criteria provided, single submitter	Mar 30, 2021	RCV003224180.1
GJB2-related disorder	Pathogenic (1)	criteria provided, single submitter	Jun 6, 2023	RCV004535149.2

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.
Pathogenic (Sep 15, 2016)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	Rare genetic deafness (Autosomal recessive inheritance) Affected status: not provided Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000710856.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018	Publications: PubMed (11) PubMed: 20863150‚ 19027181‚ 11102979‚ 15365987‚ 25388846‚ 25085072‚ 23967136‚ 10376574‚ 12408072‚ 21738759‚ 25262649 Comment: The p.Ser199Phe variant in GJB2 is a common pathogenic variant in the Colombian population, where it has been reported in the homozygous state in 11 … (more) The p.Ser199Phe variant in GJB2 is a common pathogenic variant in the Colombian population, where it has been reported in the homozygous state in 11 individuals with hearing loss (Tamayo 2009). It has also been reported in >15 additional in dividuals with hearing loss who carried a second pathogenic GJB2 variant affecti ng the other allele (Green 1999, Tamayo 2009, Rodriguez-Paris 2011). In vitro fu nctional studies provide some evidence that the p.Ser199Phe variant may impact p rotein function (Xiao 2011, Ambrosi 2013). However, these types of assays may no t accurately represent biological function. This variant has been identified in 1/120100 total chromosomes by the Exome Aggregation Consortium (ExAC, http://exa c.broadinstitute.org; dbSNP rs771748289). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a rec essive carrier frequency. In summary, this variant meets criteria to be classifi ed as pathogenic for hearing loss in an autosomal recessive manner. (less) Number of individuals with the variant: 1
Pathogenic (Jun 14, 2019)	criteria provided, single submitter (Athena Diagnostics Criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Athena Diagnostics Accession: SCV001143674.1 First in ClinVar: Jan 19, 2020 Last updated: Jan 19, 2020	Publications: PubMed (17) PubMed: 10376574‚ 23967136‚ 17666888‚ 16380907‚ 15365987‚ 11102979‚ 25085072‚ 20863150‚ 19027181‚ 12408072‚ 25388846‚ 25262649‚ 21738759‚ 29773520‚ 29311818‚ 25447126‚ 25365227 Comment: The best available variant frequency is uninformative because it is below the disease allele frequency. Statistically enriched in patients compared to ethnically matched controls. Found … (more) The best available variant frequency is uninformative because it is below the disease allele frequency. Statistically enriched in patients compared to ethnically matched controls. Found in at least one symptomatic patient. Predicted to have a damaging effect on the protein. Occurs in three or more cases with a recessive pathogenic variant in the same gene. Damaging to protein function(s) relevant to disease mechanism. Moderate co-segregation with disease in multiple families, but using affected individuals only. (less)
Pathogenic (Mar 30, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Palmoplantar keratoderma-deafness syndrome Autosomal recessive nonsyndromic hearing loss 1A Autosomal dominant nonsyndromic hearing loss 3A Ichthyosis, hystrix-like, with hearing loss Knuckle pads, deafness AND leukonychia syndrome Autosomal dominant keratitis-ichthyosis-hearing loss syndrome Mutilating keratoderma Affected status: unknown Allele origin: germline	Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago Accession: SCV003920012.1 First in ClinVar: Apr 30, 2023 Last updated: Apr 30, 2023	Comment: GJB2 NM_004004.5 exon 2 p.Ser199Phe (c.596C>T): This variant has been reported in the literature in the homozygous or compound heterozygous state in numerous individuals affected … (more) GJB2 NM_004004.5 exon 2 p.Ser199Phe (c.596C>T): This variant has been reported in the literature in the homozygous or compound heterozygous state in numerous individuals affected with autosomal recessive nonsyndromic hearing loss (Green 1999 PMID:10376574, Tamayo 2009 PMID:19027181, Rodriguez-Paris 2011 PMID:21738759). This variant is present in 0.006% (2/34580) of Latino alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/13-20763125-G-A) and is present in ClinVar (Variation ID:189183). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In addition, in vitro functional studies in HeLa cells transfected with S199F have shown a deleterious effect of this variant (Ambrosi 2013 PMID:23967136; Xiao 2011 PMID:20863150). However, these studies may not accurately represent in vivo biological function. In summary, this variant is classified as pathogenic based on the data above. (less)
Pathogenic (Jun 06, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	GJB2-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004114723.1 First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023	Comment: The GJB2 c.596C>T variant is predicted to result in the amino acid substitution p.Ser199Phe. This variant has been reported as pathogenic for autosomal recessive hearing … (more) The GJB2 c.596C>T variant is predicted to result in the amino acid substitution p.Ser199Phe. This variant has been reported as pathogenic for autosomal recessive hearing loss (Green et al 1999. PubMed ID: 10376574; Table S4, Shearer et al. 2014. PubMed ID: 25262649; 2015. PubMed ID: 25388846; García-García et al. 2020. PubMed ID: 33297549; Rodriguez-Paris et al. 2011. PubMed ID: 21738759), and functional experiments have demonstrated aberrant GJB2 protein localization to the cytoplasm (Ambrosi et al. 2013. PubMed ID: 23967136). This variant is reported in 0.0058% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/13-20763125-G-A). This variant is interpreted as pathogenic. (less)
Pathogenic (Mar 24, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Revvity Omics, Revvity Accession: SCV002024271.3 First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024
Pathogenic (Sep 11, 2017)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	Deafness, autosomal recessive 1A Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV000919431.1 First in ClinVar: Jun 02, 2019 Last updated: Jun 02, 2019	Publications: PubMed (5) PubMed: 16380907‚ 11102979‚ 17666888‚ 15365987‚ 23967136 Comment: Variant summary: The GJB2 c.596C>T (p.Ser199Phe) variant involves the alteration of a conserved nucleotide and Ser199 is located in cytoplasmic region (UniProt). 5/5 in silico … (more) Variant summary: The GJB2 c.596C>T (p.Ser199Phe) variant involves the alteration of a conserved nucleotide and Ser199 is located in cytoplasmic region (UniProt). 5/5 in silico tools predict damaging outcome for this variant. This variant was found in 1/120100 control chromosomes from ExAC at a frequency of 0.0000083, which does not exceed the estimated maximal expected allele frequency of a pathogenic GJB2 variant (0.0003376). This variant has been reported in several patients with non-syndromic hearing loss in homozygous as well as in compound heterozygous state with c.35delT and GJB6 deletion and was found to be the most common pathogenic variant in Columbia (Green_1999, Prasad_2000, Azaiez_2004, Snoeckx_2005, Putcha_2007, Tamayo_2009, Rodriguez-Paris_2011). Two independent functional studies showed that this variant leads to defective trafficking (Xiao_2011, Ambrosi_2013). One clinical diagnostic laboratory in ClinVar has classified this variant as likely pathogenic. Taken together, this variant is classified as pathogenic. (less)
Likely pathogenic (Feb 17, 2015)	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015)) Method: literature only	Deafness, autosomal recessive 1A (Autosomal recessive inheritance) Affected status: unknown Allele origin: unknown	Counsyl Accession: SCV000221138.2 First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022	Publications: PubMed (6) PubMed: 25085072‚ 10376574‚ 19027181‚ 20863150‚ 12408072‚ 23967136
Pathogenic (Sep 13, 2022)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV002577252.2 First in ClinVar: Oct 08, 2022 Last updated: Mar 04, 2023	Comment: Published functional studies demonstrate impaired membrane targeting, aberrant cellular localization, and intracellular aggregation (Xiao et al., 2011; Ambrosi et al., 2013); In silico analysis supports … (more) Published functional studies demonstrate impaired membrane targeting, aberrant cellular localization, and intracellular aggregation (Xiao et al., 2011; Ambrosi et al., 2013); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25262649, 10376574, 25388846, 11102979, 15365987, 12408072, 20863150, 25999548, 21738759, 19027181, 25085072, 29311818, 31160754, 31589614, 33297549, 23967136) (less)
Pathogenic (Jan 30, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001202556.5 First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024	Publications: PubMed (4) PubMed: 15365987‚ 19027181‚ 20863150‚ 23967136 Comment: This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 199 of the GJB2 protein (p.Ser199Phe). … (more) This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 199 of the GJB2 protein (p.Ser199Phe). This variant is present in population databases (rs771748289, gnomAD 0.006%). This missense change has been observed in individuals with autosomal recessive nonsyndromic deafness (PMID: 15365987, 19027181). ClinVar contains an entry for this variant (Variation ID: 189183). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change affects GJB2 function (PMID: 20863150, 23967136). For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001739925.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021
Pathogenic (-)	no assertion criteria provided Method: clinical testing	not provided 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: SCV001959713.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021
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Comment:

The p.Ser199Phe variant in GJB2 is a common pathogenic variant in the Colombian population, where it has been reported in the homozygous state in 11 individuals with hearing loss (Tamayo 2009). It has also been reported in >15 additional in dividuals with hearing loss who carried a second pathogenic GJB2 variant affecti ng the other allele (Green 1999, Tamayo 2009, Rodriguez-Paris 2011). In vitro fu nctional studies provide some evidence that the p.Ser199Phe variant may impact p rotein function (Xiao 2011, Ambrosi 2013). However, these types of assays may no t accurately represent biological function. This variant has been identified in 1/120100 total chromosomes by the Exome Aggregation Consortium (ExAC, http://exa c.broadinstitute.org; dbSNP rs771748289). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a rec essive carrier frequency. In summary, this variant meets criteria to be classifi ed as pathogenic for hearing loss in an autosomal recessive manner.

Comment:

The best available variant frequency is uninformative because it is below the disease allele frequency. Statistically enriched in patients compared to ethnically matched controls. Found in at least one symptomatic patient. Predicted to have a damaging effect on the protein. Occurs in three or more cases with a recessive pathogenic variant in the same gene. Damaging to protein function(s) relevant to disease mechanism. Moderate co-segregation with disease in multiple families, but using affected individuals only.

Comment:

GJB2 NM_004004.5 exon 2 p.Ser199Phe (c.596C>T): This variant has been reported in the literature in the homozygous or compound heterozygous state in numerous individuals affected with autosomal recessive nonsyndromic hearing loss (Green 1999 PMID:10376574, Tamayo 2009 PMID:19027181, Rodriguez-Paris 2011 PMID:21738759). This variant is present in 0.006% (2/34580) of Latino alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/13-20763125-G-A) and is present in ClinVar (Variation ID:189183). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In addition, in vitro functional studies in HeLa cells transfected with S199F have shown a deleterious effect of this variant (Ambrosi 2013 PMID:23967136; Xiao 2011 PMID:20863150). However, these studies may not accurately represent in vivo biological function. In summary, this variant is classified as pathogenic based on the data above.

Comment:

The GJB2 c.596C>T variant is predicted to result in the amino acid substitution p.Ser199Phe. This variant has been reported as pathogenic for autosomal recessive hearing loss (Green et al 1999. PubMed ID: 10376574; Table S4, Shearer et al. 2014. PubMed ID: 25262649; 2015. PubMed ID: 25388846; García-García et al. 2020. PubMed ID: 33297549; Rodriguez-Paris et al. 2011. PubMed ID: 21738759), and functional experiments have demonstrated aberrant GJB2 protein localization to the cytoplasm (Ambrosi et al. 2013. PubMed ID: 23967136). This variant is reported in 0.0058% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/13-20763125-G-A). This variant is interpreted as pathogenic.

Comment:

Variant summary: The GJB2 c.596C>T (p.Ser199Phe) variant involves the alteration of a conserved nucleotide and Ser199 is located in cytoplasmic region (UniProt). 5/5 in silico tools predict damaging outcome for this variant. This variant was found in 1/120100 control chromosomes from ExAC at a frequency of 0.0000083, which does not exceed the estimated maximal expected allele frequency of a pathogenic GJB2 variant (0.0003376). This variant has been reported in several patients with non-syndromic hearing loss in homozygous as well as in compound heterozygous state with c.35delT and GJB6 deletion and was found to be the most common pathogenic variant in Columbia (Green_1999, Prasad_2000, Azaiez_2004, Snoeckx_2005, Putcha_2007, Tamayo_2009, Rodriguez-Paris_2011). Two independent functional studies showed that this variant leads to defective trafficking (Xiao_2011, Ambrosi_2013). One clinical diagnostic laboratory in ClinVar has classified this variant as likely pathogenic. Taken together, this variant is classified as pathogenic.

Comment:

Published functional studies demonstrate impaired membrane targeting, aberrant cellular localization, and intracellular aggregation (Xiao et al., 2011; Ambrosi et al., 2013); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25262649, 10376574, 25388846, 11102979, 15365987, 12408072, 20863150, 25999548, 21738759, 19027181, 25085072, 29311818, 31160754, 31589614, 33297549, 23967136)

Comment:

This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 199 of the GJB2 protein (p.Ser199Phe). This variant is present in population databases (rs771748289, gnomAD 0.006%). This missense change has been observed in individuals with autosomal recessive nonsyndromic deafness (PMID: 15365987, 19027181). ClinVar contains an entry for this variant (Variation ID: 189183). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change affects GJB2 function (PMID: 20863150, 23967136). For these reasons, this variant has been classified as Pathogenic.

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:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Frequency of GJB2 mutations in patients with nonsyndromic hearing loss from an ethnically characterized Brazilian population.	Felix F	Brazilian journal of otorhinolaryngology	2019	PMID: 29773520
DFNB1 Non-syndromic Hearing Impairment: Diversity of Mutations and Associated Phenotypes.	Del Castillo FJ	Frontiers in molecular neuroscience	2017	PMID: 29311818
Bioinformatic Analysis of GJB2 Gene Missense Mutations.	Yilmaz A	Cell biochemistry and biophysics	2015	PMID: 25388846
Understanding of the molecular evolution of deafness-associated pathogenic mutations of connexin 26.	Han XH	Genetica	2014	PMID: 25447126
Atomic force microscopy shows connexin26 hemichannel clustering in purified membrane fragments.	Meckes B	Biochemistry	2014	PMID: 25365227
Utilizing ethnic-specific differences in minor allele frequency to recategorize reported pathogenic deafness variants.	Shearer AE	American journal of human genetics	2014	PMID: 25262649
Frequency of GJB2 and del(GJB6-D13S1830) mutations among an Ecuadorian mestizo population.	Paz-y-Miño C	International journal of pediatric otorhinolaryngology	2014	PMID: 25085072
Analysis of trafficking, stability and function of human connexin 26 gap junction channels with deafness-causing mutations in the fourth transmembrane helix.	Ambrosi C	PloS one	2013	PMID: 23967136
Allele-specific impairment of GJB2 expression by GJB6 deletion del(GJB6-D13S1854).	Rodriguez-Paris J	PloS one	2011	PMID: 21738759
Impaired membrane targeting and aberrant cellular localization of human Cx26 mutants associated with inherited recessive hearing loss.	Xiao Z	Acta oto-laryngologica	2011	PMID: 20863150
Molecular studies in the GJB2 gene (Cx26) among a deaf population from Bogotá, Colombia: results of a screening program.	Tamayo ML	International journal of pediatric otorhinolaryngology	2009	PMID: 19027181
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
GJB2 mutations and degree of hearing loss: a multicenter study.	Snoeckx RL	American journal of human genetics	2005	PMID: 16380907
GJB2: the spectrum of deafness-causing allele variants and their phenotype.	Azaiez H	Human mutation	2004	PMID: 15365987
Clinical presentation of DFNB1.	McGuirt WT	Advances in oto-rhino-laryngology	2002	PMID: 12408072
Genetic testing for hereditary hearing loss: connexin 26 (GJB2) allele variants and two novel deafness-causing mutations (R32C and 645-648delTAGA).	Prasad S	Human mutation	2000	PMID: 11102979
Carrier rates in the midwestern United States for GJB2 mutations causing inherited deafness.	Green GE	JAMA	1999	PMID: 10376574
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Text-mined citations for rs771748289 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 10, 2024

ClinVar Genomic variation as it relates to human health

NM_004004.6(GJB2):c.596C>T (p.Ser199Phe)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs771748289 ...