ClinVar Genomic variation as it relates to human health
NM_004004.6(GJB2):c.551G>C (p.Arg184Pro)
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.
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(11); Uncertain significance(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_004004.6(GJB2):c.551G>C (p.Arg184Pro)
Variation ID: 17007 Accession: VCV000017007.65
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 13q12.11 13: 20189031 (GRCh38) [ NCBI UCSC ] 13: 20763170 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Dec 3, 2013 Apr 20, 2024 Apr 4, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_004004.6:c.551G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003995.2:p.Arg184Pro missense NC_000013.11:g.20189031C>G NC_000013.10:g.20763170C>G NG_008358.1:g.8945G>C LRG_1350:g.8945G>C LRG_1350t1:c.551G>C LRG_1350p1:p.Arg184Pro P29033:p.Arg184Pro - Protein change
- R184P
- Other names
- -
- Canonical SPDI
- NC_000013.11:20189030:C:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- loss_of_function_variant Sequence Ontology [SO:0002054]
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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.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00006
The Genome Aggregation Database (gnomAD) 0.00003
Trans-Omics for Precision Medicine (TOPMed) 0.00005
Exome Aggregation Consortium (ExAC) 0.00004
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 | ||
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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. |
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GJB2 | Dosage sensitivity unlikely | No evidence available |
GRCh38 GRCh37 |
556 | 617 |
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. |
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Pathogenic (7) |
criteria provided, multiple submitters, no conflicts
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Oct 18, 2018 | RCV000018531.50 | |
Pathogenic (1) |
criteria provided, single submitter
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Aug 26, 2022 | RCV000211781.14 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Jan 16, 2024 | RCV000657913.25 | |
Pathogenic (1) |
no assertion criteria provided
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Jun 1, 2015 | RCV000678888.9 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 31, 2018 | RCV000763321.10 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 26, 2019 | RCV001112462.17 | |
Pathogenic (1) |
criteria provided, single submitter
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Aug 31, 2020 | RCV001257160.9 | |
Uncertain significance (1) |
criteria provided, single submitter
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Apr 4, 2024 | RCV003992158.1 |
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. |
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Pathogenic
(Mar 23, 2016)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 1A
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000698267.1
First in ClinVar: Sep 19, 2017 Last updated: Sep 19, 2017 |
Comment:
Variant summary: Variant affects a conserved nucleotide and results in a replacement of a large size and basic Arginine (R) with a medium size and … (more)
Variant summary: Variant affects a conserved nucleotide and results in a replacement of a large size and basic Arginine (R) with a medium size and hydrophobic Proline (P). 5/5 in silico tools predict the variant to be disease causing. The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 0.00412% which does not exceed the maximal expected allele frequency of a disease causing GJB2 allele (2.5%). The variant was reported in several patients affected with hearing loss, most of them were homozygous for the variant of interest or compound heterozygotes with another pathogenic GJB2 mutation indicating pathogenicity. A functional study demonstrated R184P as a coupling deficient variant. In experiments with oligomerization of mutated connexin proteins R184P was detected only as monomeric protein, suggesting inability to form hemichannels further supporting pathogenicity. Additionally, several clinical diagnostic laboratories and reputable database classify variant as pathogenic (without evidence to independently evaluate). Furthermore, variants affecting the same codon, p.R184W, p.R184G and p.R184Q were reported to be associated with Deafness, autosomal recessive 1 and Deafness, autosomal dominant 3, respectively indicating the variant to be located in a mutational hotspot and the Arg184 residue to be functionally important. Considering all evidence, the variant was classified as a Pathogenic. (less)
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Pathogenic
(Oct 31, 2018)
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criteria provided, single submitter
Method: clinical testing
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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
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000893998.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
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Pathogenic
(Oct 18, 2018)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 1A
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000914611.1
First in ClinVar: May 27, 2019 Last updated: May 27, 2019 |
Comment:
Across a selection of the available literature, GJB2 the c.551G>C (p.Arg184Pro) missense variant has been identified in a sixteen individuals affected with hearing loss including … (more)
Across a selection of the available literature, GJB2 the c.551G>C (p.Arg184Pro) missense variant has been identified in a sixteen individuals affected with hearing loss including three homozygotes, ten compound heterozygotes, and three heterozygotes (Murgia et al. 1999; Azaiez et al. 2004; Tang et al. 2006; Mani et al. 2009; Dodson et al. 2011; Keivani et al. 2015). The variant was also identified in six unaffected heterozygotes (Keivani et al. 2015). The p.Arg184Pro variant was absent from 355 controls but is reported at a frequency of 0.000087 in the Latino population of the Genome Aggregation Database. In vitro functional studies in HeLa cells showed that the p.Arg184Pro variant resulted in defective trafficking, exhibited increased RNA expression versus wild type and resulted in a coupling defect (Mani et al. 2009; Thönnissen et al. 2002). In Xenopus oocytes the variant protein was unable to induce formation of intracellular channels thus resulting in a loss of function (Bruzzone et al. 2003). Based on the collective evidence, the p.Arg184Pro variant is classified as pathogenic for autosomal recessive nonsyndromic hearing loss. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
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Pathogenic
(Jan 26, 2019)
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criteria provided, single submitter
Method: clinical testing
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Autosomal dominant nonsyndromic hearing loss 3A
Affected status: yes
Allele origin:
unknown
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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001366460.2
First in ClinVar: Jul 04, 2020 Last updated: Dec 12, 2020 |
Comment:
This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PM2,PP2,PP3,PP5.
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Pathogenic
(Jul 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Athena Diagnostics Inc
Accession: SCV001476380.1
First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021 |
Comment:
The frequency of this variant in the general population is consistent with pathogenicity. Found in at least one patient with expected phenotype for this gene. … (more)
The frequency of this variant in the general population is consistent with pathogenicity. Found in at least one patient with expected phenotype for this gene. Predicted to have a damaging effect on the protein. Other pathogenic or likely pathogenic variants affect the same amino acid. In multiple individuals, this variant has been seen with a single recessive pathogenic variant in the same gene, suggesting this variant may also be pathogenic. Assessment of experimental evidence suggests this variant results in abnormal protein function. Strong co-segregation with disease, and data include affected and unaffected individuals from multiple families. (less)
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Pathogenic
(Nov 25, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000885514.4
First in ClinVar: Feb 17, 2019 Last updated: Jan 08, 2022 |
Comment:
The GJB2 c.551G>C; p.Arg184Pro variant (rs80338950) has been described in a homozygous or compound heterozygous state in several individuals and families with nonsyndomic hearing loss … (more)
The GJB2 c.551G>C; p.Arg184Pro variant (rs80338950) has been described in a homozygous or compound heterozygous state in several individuals and families with nonsyndomic hearing loss (Denoyelle 1997, Dodson 2011, Keivani 2015). In addition, functional assays suggest that this variant impairs membrane trafficking, intercellular coupling, and hemichannel formation (Bruzzone 2003, Mani 2009, Thonnissen 2002). This variant is reported as pathogenic in ClinVar (Variation ID: 17007), and is observed in the general population at a low allele frequency of 0.006% (17/282684 alleles) in the Genome Aggregation Database. The arginine at codon 184 is highly conserved, and computational algorithms (SIFT, PolyPhen2) predict this variant to be damaging to the protein. Additionally, other amino acid substitutions at this codon (Gln, Gly, Trp) have been reported in individuals with hearing loss and are considered disease-causing (Pang 2014, Wang 2000, Zoll 2003). Based on the above information, p.Arg184Pro is considered pathogenic for autosomal recessive hearing loss. References: Bruzzone R et al. Loss-of-function and residual channel activity of connexin26 mutations associated with non-syndromic deafness. FEBS Lett. 2003 Jan 2;533(1-3):79-88. Denoyelle F et al. Prelingual deafness: high prevalence of a 30delG mutation in the connexin 26 gene. Hum Mol Genet. 1997 Nov;6(12):2173-7. Dodson KM et al. Vestibular dysfunction in DFNB1 deafness. Am J Med Genet A. 2011 May;155A(5):993-1000. Keivani A et al. A new compound heterozygous mutation in GJB2 causes nonsyndromic hearing loss in a consanguineous Iranian family. Int J Pediatr Otorhinolaryngol. 2015 Apr;79(4):553-6. Mani RS et al. Functional consequences of novel connexin 26 mutations associated with hereditary hearing loss. Eur J Hum Genet. 2009 Apr;17(4):502-9. Pang X et al. Characterization of spectrum, de novo rate and genotype-phenotype correlation of dominant GJB2 mutations in Chinese hans. PLoS One. 2014 Jun 19;9(6):e100483. Thonnissen E et al. Human connexin26 (GJB2) deafness mutations affect the function of gap junction channels at different levels of protein expression. Hum Genet. 2002 Aug;111(2):190-7. Wilcox SA et al. High frequency hearing loss correlated with mutations in the GJB2 gene. Hum Genet. 2000 Apr;106(4):399-405. Zoll B et al. Evaluation of Cx26/GJB2 in German hearing impaired persons: mutation spectrum and detection of disequilibrium between M34T (c.101T>C) and -493del10. Hum Mutat. 2003 Jan;21(1):98. (less)
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Pathogenic
(Feb 07, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000779679.4
First in ClinVar: Jul 09, 2018 Last updated: Mar 04, 2023 |
Comment:
Published functional studies demonstrate a damaging effect; variant results in the failure of intracellular coupling and gap junction channel formation (Thnnissen et al., 2002; Bruzzone … (more)
Published functional studies demonstrate a damaging effect; variant results in the failure of intracellular coupling and gap junction channel formation (Thnnissen et al., 2002; Bruzzone et al., 2003); A different missense change at this residue (p.(R184W) has been reported as pathogenic in the published literature and at GeneDxin association with autosomal recessive GJB2-related hearing loss (Wilcox et al., 2000); 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: 24529908, 15967879, 17485979, 12176179, 11551103, 22808909, 15666300, 9336442, 15855033, 12417772, 19173109, 15365987, 19715472, 19941053, 18560174, 19371219, 19125024, 14985372, 26381000, 17935238, 16380907, 21465647, 18941476, 12505163, 22975760, 10544226, 25388846, 26117665, 25085637, 17666888, 31980526, 32300592, 12176036, 34426522, 33096615, 31589614, 32067424, 10874298, 12189493, 25708704, 17041943, 27535533, 24158611, 10982180, 10830906) (less)
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Pathogenic
(Jan 16, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000935561.6
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 184 of the GJB2 protein (p.Arg184Pro). … (more)
This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 184 of the GJB2 protein (p.Arg184Pro). This variant is present in population databases (rs80338950, gnomAD 0.009%). This missense change has been observed in individuals with autosomal recessive nonsyndromic deafness (PMID: 10874298, 18941476, 19371219, 25708704, 26117665). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 17007). 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: 12176036, 12189493, 12505163, 15241677, 18941476). For these reasons, this variant has been classified as Pathogenic. (less)
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Uncertain significance
(Apr 04, 2024)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 1A
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004809807.1
First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024 |
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Pathogenic
(May 09, 2017)
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criteria provided, single submitter
Method: clinical testing
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Deafness, autosomal recessive 1A
Affected status: yes
Allele origin:
germline
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Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia
Accession: SCV000599760.1
First in ClinVar: Sep 19, 2017 Last updated: Sep 19, 2017 |
Number of individuals with the variant: 2
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Pathogenic
(Aug 31, 2020)
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criteria provided, single submitter
Method: clinical testing
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Nonsyndromic hearing loss and deafness
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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INGEBI, INGEBI / CONICET
Accession: SCV001433678.1
First in ClinVar: Sep 27, 2020 Last updated: Sep 27, 2020 |
Comment:
Based on ACMG/AMP guidelines and Hearing Loss Expert Panel specific criteria: the filter allele frequency of c.551G>C, p.Arg184Pro variant in GJB2 gene is 0,0038% (4/35426 … (more)
Based on ACMG/AMP guidelines and Hearing Loss Expert Panel specific criteria: the filter allele frequency of c.551G>C, p.Arg184Pro variant in GJB2 gene is 0,0038% (4/35426 Latino alleles with 95% CI) from Genome Aggregation Database (http://gnomad.broadinstitute.org; calculated by using inverse allele frequency at https://www.cardiodb.org/allelefrequencyapp/), which meets the PM2 criteria. This variant was identified at least in five individuals in trans with several known pathogenic variants (PM3_VeryStrong; PMID: 24158611, 10874298, 10982180, 11551103, 12176179, 16380907, 16380907, 17485979). Computational evidence predicted a damage impact of the mutation to the protein meeting PP3 rule (REVELscore: 0,983) Functional studies demonstrated that: mutant protein is neither trafficked to membrane nor able to oligomerize efficiently and unable to form functional GJCh in HeLa cells (PMID: 12176036, 1218943). Moreover, p.Arg184Pro mutant did not induce the formation of homotypic junctional channels, since the levels of conductance measured never exceeded background values in Xenopus laevis oocytes (PMID: 12505163), PS3_Moderate Therefore, this variant meets criteria to be classified as pathogenic for autosomal recessive non-syndromic hearing loss (PM2, PM3_VeryStrong, PP3 and PS3_Moderate). (less)
Number of individuals with the variant: 4
Clinical Features:
Prelingual moderate to profound hearing loss (present)
Family history: no
Sex: mixed
Ethnicity/Population group: Caucasian
Geographic origin: Argentina
Tissue: blood
Secondary finding: no
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Pathogenic
(Aug 26, 2022)
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criteria provided, single submitter
Method: clinical testing
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Rare genetic deafness
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000061525.6
First in ClinVar: May 03, 2013 Last updated: Apr 20, 2024 |
Comment:
The p.Arg184Pro variant in GJB2 has been identified in the homozygous or compound heterozygous state in more than 50 individuals with hearing loss, and in … (more)
The p.Arg184Pro variant in GJB2 has been identified in the homozygous or compound heterozygous state in more than 50 individuals with hearing loss, and in vitro functional studies provide some evidence that this variant may impact protein function (Thonnissen 2002 PMID: 12189493, Bruzzone 2003 PMID: 12505163, Mani 2009 PMID: 18941476). This variant has been identified in 1/11568 of Latino chromosomes, 1/16592 of South Asian chromosomes, and 3/67458 of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs80338950). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. In summary, the p.Arg184Pro variant meets our criteria to be classified as pathogenic for autosomal recessive hearing loss based upon strong association with the disease, low frequency in the general population, and supportive functional evidence. ACMG/AMP criteria applied: PM3_VeryStrong, PM2_Supporting, PP3, PS3_Supporting. (less)
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Pathogenic
(Feb 01, 2004)
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no assertion criteria provided
Method: literature only
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DEAFNESS, AUTOSOMAL RECESSIVE 1A
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000038813.6
First in ClinVar: Apr 04, 2013 Last updated: Sep 19, 2017 |
Comment on evidence:
For discussion of the arg184-to-pro (R184P) mutation in the GJB2 gene that was found in compound heterozygous state in 2 sisters with autosomal recessive deafness … (more)
For discussion of the arg184-to-pro (R184P) mutation in the GJB2 gene that was found in compound heterozygous state in 2 sisters with autosomal recessive deafness (DFNB1A; 220290) by Denoyelle et al. (1997), see 121011.0007. In an 18-month-old Arab Israeli boy with nonsyndromic hearing impairment, Shalev and Hujirat (2004) screened the GJB2 gene for mutations known to occur in the Arab population and identified the 35delG (121011.0005) and R184P mutations. The father was a carrier of 35delG and the mother was negative for both mutations; however, biparental contribution was confirmed by segregation analysis. Shalev and Hujirat (2004) stated that this case represented the first report of a de novo mutation in the GJB2 gene leading to recessive nonsyndromic hearing impairment, and was particularly unusual because the new mutation occurred on the maternal allele. (less)
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Pathogenic
(Jun 01, 2015)
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no assertion criteria provided
Method: clinical testing
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Hearing loss
Affected status: yes
Allele origin:
germline
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Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital
Accession: SCV000805081.1
First in ClinVar: Sep 14, 2018 Last updated: Sep 14, 2018 |
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Pathogenic
(Sep 09, 2016)
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no assertion criteria provided
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 1A
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000220825.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 23, 2019 |
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Pathogenic
(Aug 12, 2020)
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no assertion criteria provided
Method: clinical testing
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Autosomal recessive deafness type 1A
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002094996.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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not provided
(-)
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no classification provided
Method: literature only
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Autosomal recessive nonsyndromic hearing loss 1A
Affected status: not provided
Allele origin:
unknown
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GeneReviews
Accession: SCV000041050.3
First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2022 |
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Germline Functional Evidence
Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for 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 functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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loss_of_function_variant
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INGEBI, INGEBI / CONICET
Accession: SCV001433678.1
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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GJB2-Related Autosomal Recessive Nonsyndromic Hearing Loss. | Adam MP | - | 2023 | PMID: 20301449 |
Molecular epidemiology of Chinese Han deaf patients with bi-allelic and mono-allelic GJB2 mutations. | Yu X | Orphanet journal of rare diseases | 2020 | PMID: 31992338 |
First-Line Molecular Genetic Evaluation of Autosomal Recessive Non-Syndromic Hearing Loss. | Özyılmaz B | Turkish archives of otorhinolaryngology | 2019 | PMID: 31620696 |
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 |
The controversial p.Met34Thr variant in GJB2 gene: Two siblings, one genotype, two phenotypes. | Lameiras AR | International journal of pediatric otorhinolaryngology | 2015 | PMID: 26117665 |
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 |
Spectrum and frequency of GJB2 mutations causing deafness in the northwest of Iran. | Bonyadi MJ | International journal of pediatric otorhinolaryngology | 2014 | PMID: 24529908 |
Identification of four novel connexin 26 mutations in non-syndromic deaf patients: genotype-phenotype analysis in moderate cases. | Dalamón V | Molecular biology reports | 2013 | PMID: 24158611 |
An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: results from an ethnically diverse clinical sample of 23,453 individuals. | Lazarin GA | Genetics in medicine : official journal of the American College of Medical Genetics | 2013 | PMID: 22975760 |
Molecular and hereditary mechanisms of sensorineural hearing loss with focus on selected endocrinopathies. | Masindova I | Endocrine regulations | 2012 | PMID: 22808909 |
Vestibular dysfunction in DFNB1 deafness. | Dodson KM | American journal of medical genetics. Part A | 2011 | PMID: 21465647 |
Spectrum of CFTR gene mutations in Iranian Azeri Turkish patients with cystic fibrosis. | Bonyadi M | Genetic testing and molecular biomarkers | 2011 | PMID: 21198395 |
Two novel missense mutations in the connexin 26 gene in Turkish patients with nonsyndromic hearing loss. | Yilmaz A | Biochemical genetics | 2010 | PMID: 19941053 |
Mutation analysis of familial GJB2-related deafness in Iranian Azeri Turkish patients. | Bonyadi M | Genetic testing and molecular biomarkers | 2009 | PMID: 19715472 |
Analysis of the GJB2 and GJB6 genes in Italian patients with nonsyndromic hearing loss: frequencies, novel mutations, genotypes, and degree of hearing loss. | Primignani P | Genetic testing and molecular biomarkers | 2009 | PMID: 19371219 |
Hearing loss features in GJB2 biallelic mutations and GJB2/GJB6 digenic inheritance in a large Italian cohort. | Cama E | International journal of audiology | 2009 | PMID: 19173109 |
Prevalence of GJB2 (connexin-26) and GJB6 (connexin-30) mutations in a cohort of 300 Brazilian hearing-impaired individuals: implications for diagnosis and genetic counseling. | Batissoco AC | Ear and hearing | 2009 | PMID: 19125024 |
Functional consequences of novel connexin 26 mutations associated with hereditary hearing loss. | Mani RS | European journal of human genetics : EJHG | 2009 | PMID: 18941476 |
GJB2 and mitochondrial A1555G gene mutations in nonsyndromic profound hearing loss and carrier frequencies in healthy individuals. | Baysal E | Journal of genetics | 2008 | PMID: 18560174 |
M34T and V37I mutations in GJB2 associated hearing impairment: evidence for pathogenicity and reduced penetrance. | Pollak A | American journal of medical genetics. Part A | 2007 | PMID: 17935238 |
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 |
High incidence of GJB2 mutations during screening of newborns for hearing loss in Austria. | Ramsebner R | Ear and hearing | 2007 | PMID: 17485979 |
DNA sequence analysis of GJB2, encoding connexin 26: observations from a population of hearing impaired cases and variable carrier rates, complex genotypes, and ethnic stratification of alleles among controls. | Tang HY | American journal of medical genetics. Part A | 2006 | PMID: 17041943 |
GJB2 mutations and degree of hearing loss: a multicenter study. | Snoeckx RL | American journal of human genetics | 2005 | PMID: 16380907 |
GJB2 and GJB6 mutations: genotypic and phenotypic correlations in a large cohort of hearing-impaired patients. | Marlin S | Archives of otolaryngology--head & neck surgery | 2005 | PMID: 15967879 |
GJB2 mutations in Turkish patients with ARNSHL: prevalence and two novel mutations. | Kalay E | Hearing research | 2005 | PMID: 15855033 |
GJB2: the spectrum of deafness-causing allele variants and their phenotype. | Azaiez H | Human mutation | 2004 | PMID: 15365987 |
Altered gating properties of functional Cx26 mutants associated with recessive non-syndromic hearing loss. | Meşe G | Human genetics | 2004 | PMID: 15241677 |
A genotype-phenotype correlation for GJB2 (connexin 26) deafness. | Cryns K | Journal of medical genetics | 2004 | PMID: 14985372 |
Maternal origin of a de novo mutation of the connexin 26 gene resulting in recessive nonsyndromic deafness. | Shalev SA | American journal of medical genetics. Part A | 2004 | PMID: 14735592 |
Loss-of-function and residual channel activity of connexin26 mutations associated with non-syndromic deafness. | Bruzzone R | FEBS letters | 2003 | PMID: 12505163 |
Prelingual nonsyndromic hearing loss in Greece. Molecular and clinical findings. | Iliades T | ORL; journal for oto-rhino-laryngology and its related specialties | 2002 | PMID: 12417772 |
Human connexin26 (GJB2) deafness mutations affect the function of gap junction channels at different levels of protein expression. | Thönnissen E | Human genetics | 2002 | PMID: 12189493 |
Prevalence of GJB2 mutations in prelingual deafness in the Greek population. | Pampanos A | International journal of pediatric otorhinolaryngology | 2002 | PMID: 12176179 |
Hearing loss: frequency and functional studies of the most common connexin26 alleles. | D'Andrea P | Biochemical and biophysical research communications | 2002 | PMID: 12176036 |
High frequency of GJB2 gene mutations in Polish patients with prelingual nonsyndromic deafness. | Wiszniewski W | Genetic testing | 2001 | PMID: 11551103 |
Molecular basis of childhood deafness resulting from mutations in the GJB2 (connexin 26) gene. | Rabionet R | Human genetics | 2000 | PMID: 10982180 |
Mutation analysis of the GJB2 (connexin 26) gene by DGGE in Greek patients with sensorineural deafness. | Antoniadi T | Human mutation | 2000 | PMID: 10874298 |
Cx26 deafness: mutation analysis and clinical variability. | Murgia A | Journal of medical genetics | 1999 | PMID: 10544226 |
Connexin 26 gene linked to a dominant deafness. | Denoyelle F | Nature | 1998 | PMID: 9620796 |
Prelingual deafness: high prevalence of a 30delG mutation in the connexin 26 gene. | Denoyelle F | Human molecular genetics | 1997 | PMID: 9336442 |
Progress in vascular surgery (a report of experience over two decades). | Pandey SR | Indian journal of medical sciences | 1975 | PMID: 1218943 |
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Text-mined citations for rs80338950 ...
HelpRecord last updated Apr 20, 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.