ClinVar Miner

Submissions for variant NM_004004.6(GJB2):c.341A>G (p.Glu114Gly) (rs2274083)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000037838 SCV000061500 benign not specified 2014-08-14 criteria provided, single submitter clinical testing Glu114Gly in exon 2 of GJB2: This variant is not expected to have clinical signi ficance because it has been identified in 10-20% Asian chromosomes by several st udies (http://www.1000genomes.org; dbSNP rs2274083; Park 2000, Choung 2002, Watt anasirichaigoon 2004, Tekin 2010, Tsukada 2010, Wei 2013).
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000037838 SCV000112267 benign not specified 2014-11-14 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV000037838 SCV000193168 benign not specified 2013-02-08 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000037838 SCV000309914 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000505536 SCV000383014 benign Deafness, autosomal recessive 1A 2018-03-06 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx RCV000037838 SCV000513147 benign not specified 2016-06-27 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.
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000505536 SCV000599746 benign Deafness, autosomal recessive 1A 2017-05-09 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000037838 SCV000603814 benign not specified 2019-04-15 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588130 SCV000698246 benign not provided 2016-04-13 criteria provided, single submitter clinical testing Variant summary: The c.341A>G (p.E114G) in GJB2 gene is a missense change that alters a non-conserved nucleotide and 4/5 in silico tools predict benign outcome. The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 1.5%, predominantly in individuals of East Asian descent (18,8%) including numerous homozygous occurrences. This frequency suggests that the variant is a common ethnic-specific functional polymorphism. The variant has been reported to be mainly found in complex form (in cis with V27I) and in trans with V27I ( as well as with other variants) in both affected and unaffected individuals. Ogawa et al., (2014) report this complex variant to be found in unaffected individual who also carried p.Y136X on the other allele. In several patients reported by Dai et al, this variant occurred as complex forms p.[E114G;V27I] and [E114G;V27I;R127H] in compound heterozygosity swith known pathogenic variants, such as c.35delG, c.235delC, c.299_300delAT,Y125X, and c.424_426delTTC. Of typical observation, two patients were compound heterozygous for this variant and c.235delC. Furthermore, the complex p.[E114G;V27I] also co-occurred in cis with a known pathogenic variant (V37I) in four patients suggesting this complex is not pathogenic. Several independent groups showed that E114 in isolation or in complex with V27I formed gap junctions comparable to controls. In the field, this variant is widely accepted to be a polymorphism (Shearer et al., 2014). Taken together, the variant was classified as Benign.
Athena Diagnostics Inc RCV000588130 SCV000841704 benign not provided 2017-11-29 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001112559 SCV001270223 benign Deafness, autosomal dominant 3a 2018-03-06 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV001112560 SCV001270224 benign Hystrix-like ichthyosis with deafness 2018-03-06 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

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