ClinVar Miner

Submissions for variant NM_004004.6(GJB2):c.169C>T (p.Gln57Ter) (rs111033297)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000211761 SCV000061477 pathogenic Rare genetic deafness 2007-10-25 criteria provided, single submitter clinical testing The Gln57X variant in GJB2 has been reported in at least 20 individuals with hea ring loss (Dodson 2011, Feldmann 2004, Marlin 2005, Roux 2004, Snoeckx 2005, Wil cox 1999). Most of these individuals were homozygous or compound heterozygous. I t has also been identified in 0.007% (9/128912) of European chromosomes by gnomA D (http://gnomad.broadinstitute.org). This nonsense variant leads to a premature termination codon at position 57, which is predicted to lead to a truncated or absent protein. Loss of function of the GJB2 gene is an established disease mech anism in autosomal recessive hearing loss. In summary, this variant meets criter ia to be classified as pathogenic for autosomal recessive hearing loss. ACMG/AMP Criteria applied: PVS1, PM3_VeryStrong, PM2.
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000505512 SCV000599735 pathogenic Deafness, autosomal recessive 1A 2017-05-09 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000711347 SCV000603833 pathogenic not provided 2017-05-19 criteria provided, single submitter clinical testing The p.Gln57Ter (rs111033297) has been observed in several cohorts of patients with sensorineural hearing loss, many carrying a second pathogenic variant in GJB2 (selected references: Wilcox 1999, Snoeckx 2005, Marlin 2005). This variant introduces a premature termination codon and is predicted to result in a truncated protein product. Consistent with a recessive carrier frequency, it is listed in the Genome Aggregation Database (gnomAD) browser with an overall frequency of 0.004% (identified in 11 out of 276,670 chromosomes). It is also listed in the ClinVar database as pathogenic (Variation ID: 44725). Thus, the p.Gln57Ter variant satisfies our criteria for classification as pathogenic.
Athena Diagnostics Inc RCV000711347 SCV000841699 pathogenic not provided 2018-07-12 criteria provided, single submitter clinical testing
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000678870 SCV000805063 pathogenic Hearing loss 2009-11-12 no assertion criteria provided clinical testing
Counsyl RCV000505512 SCV001132400 pathogenic Deafness, autosomal recessive 1A 2015-10-09 no assertion criteria provided clinical testing

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