ClinVar Miner

Submissions for variant NM_004004.6(GJB2):c.384C>T (p.Ile128=)

dbSNP: rs111033298
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000037848 SCV000061510 likely benign not specified 2007-02-21 criteria provided, single submitter clinical testing
INGEBI, INGEBI / CONICET RCV001257147 SCV001433663 likely 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 c.384C>T p.(Ile128=) variant in GJB2 gene is absent from population databases (gnomAD, GO-ESP, 1000 genomes) meeting PM2 criteria. This variant has been detected in a heterozygous state in two hearing impaired patients (PMID:928500, 11102979). In a previous report we detected the p.Ile128= variant in cis with a pathogenic variant (PMID: 24158611). Since the cause of the hearing loss was the c.[35delG];[167delT] genotype, the p.(Ile128=) change is in cis with one of these alleles applying to BP2 rule. Computational evidence predicted that the mutation is not conserved between species (GERPscore:-1.12; BP4) and there is no impact on splicing (analyzed with Human Splicing Finder) meeting BP7 rule. Therefore, this variant meets criteria to be classified as likely benign for autosomal recessive non-syndromic hearing loss (PM2, BP2, BP4 and BP7).
Labcorp Genetics (formerly Invitae), Labcorp RCV001425886 SCV001628524 likely benign not provided 2024-01-31 criteria provided, single submitter clinical testing

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