Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001058334 | SCV001222894 | likely pathogenic | Charcot-Marie-Tooth Neuropathy X | 2019-05-09 | criteria provided, single submitter | clinical testing | This sequence change results in a premature translational stop signal in the GJB1 gene (p.Ser258Profs*2). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 26 amino acids of the GJB1 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with Charcot-Marie-Tooth disease (PMID: 25614874). This variant disrupts the C-terminus of the GJB1 protein. Other variant(s) that disrupt this region (p.Asp278_Cys280del, p.Ser281*, p.Cys283*) have been observed in individuals with GJB1-related conditions (PMID: 8990008, 23011429, 28768847). This suggests that this may be a clinically significant region of the protein. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Inherited Neuropathy Consortium | RCV000789213 | SCV000928565 | pathogenic | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |