ClinVar Miner

Submissions for variant NM_004004.6(GJB2):c.457G>A (p.Val153Ile) (rs111033186)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000037857 SCV000061519 benign not specified 2015-05-28 criteria provided, single submitter clinical testing p.Val153Ile in exon 2 of GJB2: This variant has been reported in the literature as both a benign polymorphism (Connexins and Deafness Website and other reports) as well as a pathogenic variant (Snoeckx 2005 and other reports). Several repor ts show that this variant occurs at an equal frequency in both hearing loss prob ands and the general population (Guerci 2007, Abidi 2008, RamShankar 2003, Roux 2004, Rickard 2001). It was also identified in 5.6% (922/16488) of South Asian c hromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute .org; dbSNP rs111033186), including 31 homozygous individuals. Functional studie s have demonstrated no impact to synthesis and localization of the connexin 26 p rotein (Guerci 2007). It has also been reported in a homozygous state in 3 indiv iduals with normal hearing (Guerci 2007, RamShankar 2003) as well as identified as a compound heterozygote in a normal hearing individual with the p.Met34Thr mu tation (Malikova 2004). And finally, this variant did not segregate with hearing loss in two kindreds (Gasmelseed 2004, Malikova 2004). In summary, these data s uggest that the p.Val153Ile variant is benign.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000037857 SCV000112274 benign not specified 2012-12-18 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000037857 SCV000193176 benign not specified 2013-02-08 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000037857 SCV000309917 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000270707 SCV000383002 likely benign Nonsyndromic Hearing Loss, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000505519 SCV000599753 benign Deafness, autosomal recessive 1A 2017-05-09 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000755275 SCV000603811 benign not provided 2017-09-24 criteria provided, single submitter clinical testing
GeneDx RCV000755275 SCV000977441 benign not provided 2018-03-27 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.
Athena Diagnostics Inc RCV000755275 SCV001143670 likely benign not provided 2018-10-03 criteria provided, single submitter clinical testing

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