ClinVar Miner

Submissions for variant NM_004004.6(GJB2):c.37G>A (p.Val13Met) (rs768130937)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000779131 SCV000915628 uncertain significance Deafness, autosomal recessive 1A 2018-11-21 criteria provided, single submitter clinical testing The GJB2 c.37G>A (p.Val13Met) missense variant was reported in a single study in a cohort of 7,401 North American individuals with hearing loss where it was found in a compound heterozygous state with a second known pathogenic missense variant in one affected individual (Putcha et al. 2007). The p.Val13Met variant occurs in a highly conserved region and is predicted by multiple prediction algorithms to be deleterious (Yilmaz et al. 2015). Control data are unavailable for this variant which is reported at a frequency of 0.00121 in the Latino population of the Exome Aggregation Consortium. Based on the limited evidence, the p.Val13Met variant is classified as a variant of unknown significance but suspicious for pathogenicity for a recessive form of nonsyndromic hearing loss. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Illumina Clinical Services Laboratory,Illumina RCV001112644 SCV001270328 likely benign Hystrix-like ichthyosis with deafness 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Clinical Services Laboratory,Illumina RCV001112645 SCV001270329 likely benign Deafness, autosomal dominant 3a 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Integrated Genetics/Laboratory Corporation of America RCV001193185 SCV001361877 uncertain significance not specified 2019-07-26 criteria provided, single submitter clinical testing Variant summary: GJB2 c.37G>A (p.Val13Met) results in a conservative amino acid change located in the Connexin, N-terminal domain of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 9.6e-05 in 249454 control chromosomes, predominantly at a frequency of 0.00061 within the Latino subpopulation in the gnomAD database. This frequency is not significantly higher than expected for a pathogenic variant in GJB2 causing Non-Syndromic Hearing Loss (9.6e-05 vs 0.026), allowing no conclusion about variant significance. c.37G>A has been reported in the literature in one individual affected with Non-Syndromic Hearing Loss (Putcha_2007). This report does not provide unequivocal conclusions about association of the variant with Non-Syndromic Hearing Loss. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar (after 2014), classifying the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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