Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000698825 | SCV000827513 | likely pathogenic | Charcot-Marie-Tooth Neuropathy X | 2023-08-11 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Leu131 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been observed in individuals with GJB1-related conditions (PMID: 34190362), which suggests that this may be a clinically significant amino acid residue. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GJB1 protein function. ClinVar contains an entry for this variant (Variation ID: 576347). This missense change has been observed in individuals with Charcot-Marie-Tooth disease (PMID: 9818870, 12362307). 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 replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 131 of the GJB1 protein (p.Leu131Pro). |
| Mendelics | RCV002249416 | SCV002516351 | likely pathogenic | Charcot-Marie-Tooth disease X-linked dominant 1 | 2022-05-04 | criteria provided, single submitter | clinical testing | |
| Inherited Neuropathy Consortium | RCV000789284 | SCV000928637 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |