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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