Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001844224 | SCV000807821 | likely pathogenic | Nonsyndromic Deafness | 2018-03-10 | criteria provided, single submitter | clinical testing | This variant creates a premature stop signal at position 235 of the GJB3 protein, written as p.Arg235Ter or p.R235*. The substitution is predicted to result in a non-functional GJB3 protein, either through protein truncation or nonsense-mediated mRNA decay. This mutation is considered a non-tolerated amino acid change based on in silico prediction algorithms (disease causing), and it has not been reported in the ClinVar Database (NCBI National Library of Medicine, NIH), but it has been described in 3 alleles out of 119888, in the ExAC database, all of them belonging to heterozygous carries of European origin. Based on these findings and the limited literature regarding this substitution we consider it as a likely pathogenic variant. |
Invitae | RCV002531414 | SCV003510892 | uncertain significance | not provided | 2022-10-14 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 561271). This variant has not been reported in the literature in individuals affected with GJB3-related conditions. This variant is present in population databases (rs144964568, gnomAD 0.004%). This sequence change creates a premature translational stop signal (p.Arg235*) in the GJB3 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 36 amino acid(s) of the GJB3 protein. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |