Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001856232 | SCV002293644 | likely pathogenic | Charcot-Marie-Tooth Neuropathy X | 2021-12-02 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Val38 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7833935, 9354338, 12460545; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 637179). This missense change has been observed in individuals with Charcot-Marie-Tooth disease and/or clinical features of Charcot-Marie-Tooth disease (PMID: 14991359, 32010055; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 38 of the GJB1 protein (p.Val38Ala). |
| Inherited Neuropathy Consortium | RCV000789237 | SCV000928589 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |