ClinVar Miner

Submissions for variant NM_004004.6(GJB2):c.368C>A (p.Thr123Asn) (rs111033188)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000037845 SCV000061507 likely benign not specified 2011-06-09 criteria provided, single submitter clinical testing Thr123Asn in exon 2 of GJB2: This variant has been previously reported in patien ts with hearing loss as well as in control subjects as a rare polymorphism (Park 2000, Tang 2006, Cryns 2004, Dai 2009, Hwa 2003, Oguchi 2005, Ohtsuka 2003, Shi 2004, Snoeckx 2005). The allele frequencies of this variant are higher in the c ontrol group (~0.9%) than in the patient group (~0.4%), suggesting that this var iant does not have clinical significance.
PreventionGenetics,PreventionGenetics RCV000037845 SCV000309915 benign not specified criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000037845 SCV000342929 likely benign not specified 2016-06-10 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000389408 SCV000383004 likely benign Keratitis-Ichthyosis-Deafness Syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000295290 SCV000383005 likely benign Mutilating keratoderma 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000331479 SCV000383006 likely benign Hystrix-like ichthyosis with deafness 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000385674 SCV000383007 likely benign Nonsyndromic Hearing Loss, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000281969 SCV000383008 likely benign Nonsyndromic Hearing Loss, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000590041 SCV000698253 likely benign not provided 2016-02-10 criteria provided, single submitter clinical testing Variant summary: c.368C>A affects a non-conserved nucleotide, resulting in amino acid change from Thr to Asn. 3/4 in-silico tools predict this variant to be benign (SNPs&GO not captured due to low reliability index). This variant was found in 88/126520 control chromosomes at a frequency of 0.0006955, predominantly observed in East Asian subpopulation cohort with MAF of 0.007295 in ExAC with one homozygote. This frequency exceeds the maximal expected frequency of a pathogenic allele (0.0003376), suggesting this variant is benign polymorphism especially in East Asians. This variant has been reported in multiple NSHL pts (mainly East Asian ethnicity) without strong evidence for causality. Many studies have reported variant in patients with comparable frequencies (or lower than) detected in controls, further supporting the benign nature of this variant. In addition, one reputable clinical laboratory classified this variant as likely benign. Taken together, this variant was classified as probably normal variant until more evidence becomes available.
Baylor-Hopkins Center for Mendelian Genomics,Johns Hopkins University RCV000785600 SCV000924177 likely benign Deafness, autosomal dominant 3a criteria provided, single submitter research
GeneDx RCV000590041 SCV000969487 likely benign not provided 2017-01-10 criteria provided, single submitter clinical testing 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.

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