Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003581711 | SCV004299616 | uncertain significance | Charcot-Marie-Tooth Neuropathy X | 2023-07-25 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 158 of the GJB1 protein (p.Pro158Ala). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Charcot-Marie-Tooth disease (PMID: 9566397, 9818870, 26989944). ClinVar contains an entry for this variant (Variation ID: 637158). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change does not substantially affect GJB1 function (PMID: 15006706). This variant disrupts the p.Pro158 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been observed in individuals with GJB1-related conditions (PMID: 26989944, 32657593; Invitae), which suggests that this may be a clinically significant amino acid residue. 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. |
| Inherited Neuropathy Consortium | RCV000789207 | SCV000928559 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |