ClinVar

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the GJB2 protein in which other variant(s) (p.Arg216Ilefs*17) have been determined to be pathogenic (PMID: 11102979, 17041943, 17666888, 25288386). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 2137457). This premature translational stop signal has been observed in individual(s) with autosomal recessive deafness (PMID: 15617546). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu110Argfs*2) in the GJB2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 117 amino acid(s) of the GJB2 protein.