Total submissions: 22
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular 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. |
Eurofins Ntd Llc |
RCV000037857 | SCV000112274 | benign | not specified | 2012-12-18 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV000037857 | SCV000193176 | benign | not specified | 2013-02-08 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV000037857 | SCV000309917 | benign | not specified | criteria provided, single submitter | clinical testing | ||
Illumina Laboratory Services, |
RCV000270707 | SCV000383002 | benign | Autosomal dominant nonsyndromic hearing loss 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. |
Genomic Diagnostic Laboratory, |
RCV000505519 | SCV000599753 | benign | Autosomal recessive nonsyndromic hearing loss 1A | 2017-05-09 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000755275 | SCV000603811 | benign | not provided | 2023-11-27 | criteria provided, single submitter | clinical testing | |
Gene |
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 | RCV000037857 | SCV001143670 | benign | not specified | 2024-11-07 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV001109786 | SCV001267155 | benign | Ichthyosis, hystrix-like, with hearing loss | 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 Laboratory Services, |
RCV000505519 | SCV001267156 | likely benign | Autosomal recessive nonsyndromic hearing loss 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. |
INGEBI, |
RCV001257148 | SCV001433664 | benign | Nonsyndromic genetic hearing loss | 2020-08-31 | criteria provided, single submitter | clinical testing | Based on ACMG/AMP guidelines and Hearing Loss Expert Panel specific criteria: the filtering allele frequency of c.457G>A p.Val153Ile in GJB2 gene is 5% (1642/30610 Southeast Asian chromosomes with 95% CI) from Genome Aggregation Database (http://gnomad.broadinstitute.org; calculated by using inverse allele frequency at https://www.cardiodb.org/allelefrequencyapp/)), which meets the allele frequency threshold defined by the ClinGen Hearing Loss Expert Panel for considering very strong evidence against pathogenicity for autosomal recessive hearing loss variants (BA1). Functional studies demonstrated that mutants lost their abilities to form functional gap junction channels (PMID: 15241677). However, it was shown that there were not differences between p.Val153Ile mutant and wild-type results in dye transfer assay (Guerci V.I, et al 2007). Therefore, functional data was not counted. Besides, the p.Val153Ile change was detected in trans with c.35delG and in homozygous state in normal-hearing individuals applying to BS2 rule (PMID:11493200, 12746422). In summary, this variant meets criteria to be classified as benign for autosomal recessive non-syndromic hearing loss (BA1 and BS2). |
Labcorp Genetics |
RCV000755275 | SCV001718430 | benign | not provided | 2025-01-29 | criteria provided, single submitter | clinical testing | |
Pars Genome Lab | RCV000505519 | SCV001749996 | likely benign | Autosomal recessive nonsyndromic hearing loss 1A | 2021-07-01 | criteria provided, single submitter | clinical testing | |
Pars Genome Lab | RCV000270707 | SCV001749997 | benign | Autosomal dominant nonsyndromic hearing loss 3A | 2021-07-01 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002496603 | SCV002805646 | benign | Autosomal recessive nonsyndromic hearing loss 1A; Mutilating keratoderma; Ichthyosis, hystrix-like, with hearing loss; Autosomal dominant keratitis-ichthyosis-hearing loss syndrome; Palmoplantar keratoderma-deafness syndrome; Knuckle pads, deafness AND leukonychia syndrome; Autosomal dominant nonsyndromic hearing loss 3A; X-linked mixed hearing loss with perilymphatic gusher | 2022-05-11 | criteria provided, single submitter | clinical testing | |
Breakthrough Genomics, |
RCV000755275 | SCV005219302 | likely benign | not provided | criteria provided, single submitter | not provided | ||
University of Washington Center for Mendelian Genomics, |
RCV001291334 | SCV001479808 | likely pathogenic | Hearing loss, autosomal recessive | no assertion criteria provided | research | ||
Clinical Genetics, |
RCV000037857 | SCV001924668 | benign | not specified | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000037857 | SCV001960037 | benign | not specified | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000037857 | SCV001974298 | benign | not specified | no assertion criteria provided | clinical testing | ||
Natera, |
RCV000505519 | SCV002086044 | benign | Autosomal recessive nonsyndromic hearing loss 1A | 2019-11-14 | no assertion criteria provided | clinical testing |