Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001318399 | SCV001509098 | uncertain significance | Charcot-Marie-Tooth Neuropathy X | 2022-07-12 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). 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. This variant disrupts the p.Cys64 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 24768312, 27098783; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 637586). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 9187667). This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 64 of the GJB1 protein (p.Cys64Ser). |
| Inherited Neuropathy Consortium | RCV000789835 | SCV000929219 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |