Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000476759 | SCV000544769 | pathogenic | Charcot-Marie-Tooth Neuropathy X | 2016-11-30 | criteria provided, single submitter | clinical testing | This variant disrupts the final 169 amino acids, or about 60%, of the GJB1 protein. In addition, a different truncation downstream of this variant (p.Arg220*) has been determined to be pathogenic (PMID: 8162049, 9364054). This suggests that deletion of this region of the GJB1 protein is causative of disease. For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with a GJB1-related disease. This sequence change inserts 1 nucleotide in exon 2 of the GJB1 mRNA (c.343dupC), causing a frameshift at codon 115. This creates a premature translational stop signal in the last exon of the GJB1 mRNA (p.Leu115Profs*32). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 169 amino acids of the GJB1 protein. |