GJB2 M34T - GET-Evidence

Curation:
Currentness:

GJB2 M34T

(GJB2 Met34Thr)


You are viewing the latest version of this page, saved on April 8, 2016 at 1:56pm by Madeleine Ball.

Edited in this revision:

Short summary

Several labs have reported in ClinVar that this causes deafness in a recessive manner: http://www.ncbi.nlm.nih.gov/clinvar/variation/17000/ This variant seems to be “mild”, with a stronger effect when combined with a more severe variant. The variant is relatively common: according to ExAC data, 1 in 40 with European ancestry (and 1 in 25 Finnish) are carriers of this variant. Löppönen et al 2012 report that homozygotes for the variant have mild to moderate hearing impairment.

Variant evidence
Computational -
Functional -
Case/Control 5

Well established

Familial 5

Well established

 
Clinical importance
Severity 3
Treatability 1
Penetrance 5
 

Impact

Moderate clinical importance, pathogenic

(The "moderate clinical importance, " qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

recessive

Summary of published research, and additional commentary

 

Allele frequency

  • G @ chr13:20763620: 1.0% (107/10758) in EVS
  • G @ chr13:19661619: 0.8% (1/128) in GET-Evidence
  • Frequency shown in summary reports: 1.0% (107/10758)

Publications
 

Löppönen T, Dietz A, Väisänen ML, Valtonen H, Kosunen A, Hyvärinen A, Ignatius J, Löppönen H. Homozygous M34T mutation of the GJB2 gene associates with an autosomal recessive nonsyndromic sensorineural hearing impairment in Finnish families. Acta Otolaryngol. 2012 Aug;132(8):862-73. doi: 10.3109/00016489.2012.669498. Epub 2012 Jun 5. PubMed PMID: 22668073.

 

Genomes
 

GS19649 - var-GS19649-1100-36-ASM
het G @ chr13:19661620

 

Other external references
 

    dbSNP
  • rs35887622
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    GeneTests
  • GeneTests records for the GJB2 gene
    Nonsyndromic Hearing Loss and Deafness, Autosomal Recessive
    Nonsyndromic Hearing Loss and Deafness, Autosomal Dominant
    DFNA 3 Nonsyndromic Hearing Loss and Deafness
    DFNB 1 Nonsyndromic Hearing Loss and Deafness
    GJB2-Related DFNA 3 Nonsyndromic Hearing Loss and Deafness
    GJB2-Related DFNB 1 Nonsyndromic Hearing Loss and Deafness
    Ichthyosis, Hystrix-like, with Deafness
    Keratitis-Ichthyosis-Deafness Syndrome, Autosomal Dominant
    Vohwinkel Syndrome
    www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/GJB2
    PolyPhen-2
  • Score: 0.808 (possibly damaging)

Other in silico analyses
 

  • NBLOSUM100 score = 2
  • GET-Evidence autoscore = 5

Edit history
 

Gene search

"GENE" or "GENE A123C":

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