See Table A. Genes and Databases for chromosome locus and protein.

See Molecular Genetics for information on variants detected in this gene.

An additional individual with a contiguous gene deletion that includes GJB2 (not included in these calculations) has been reported (see Genetically Related Disorders).

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

Data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2020] and the ClinGen Hearing Loss Clinical Domain Working Group

If a single GJB2 variant is detected by conventional Sanger sequencing, reflexing to a next-generation sequencing-based diagnostic panel targeting the entire GJB2 gene and other known hearing loss-associated genes is highly recommended [Sloan-Heggen et al 2016].

Types of GJB2 variants that may be missed by standard sequencing-based methods include (1) intragenic deletions and deletions that include GJB2 and sequences upstream of GJB2 (comprising either GJB6 and portions of CRYL1 or just portions of CRYL1) that delete cis-regulatory regions of GJB2, thereby abolishing GJB2 expression [Abe et al 2018] and (2) mosaic UPD [Lin et al 2021]. See Molecular Genetics, GJB2-specific laboratory technical considerations.

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.