Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000792639 | SCV000931947 | pathogenic | Charcot-Marie-Tooth Neuropathy X | 2022-12-23 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gln80 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7580242, 8737658, 10737979, 17353473). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: 637563). This missense change has been observed in individuals with Charcot-Marie-Tooth disease (PMID: 22465464; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 80 of the GJB1 protein (p.Gln80Lys). |
| Ambry Genetics | RCV002424787 | SCV002731932 | uncertain significance | Inborn genetic diseases | 2022-06-17 | criteria provided, single submitter | clinical testing | The p.Q80K variant (also known as c.238C>A), located in coding exon 1 of the GJB1 gene, results from a C to A substitution at nucleotide position 238. The glutamine at codon 80 is replaced by lysine, an amino acid with similar properties. This alteration has been detected in one patient in a Charcot-Marie-Tooth neuropathy X type 1 (CMTX1) cohort; however, clinical details were limited (Arthur-Farraj PJ et al. Neuromuscul Disord, 2012 Jul;22:622-6). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Inherited Neuropathy Consortium | RCV000789802 | SCV000929186 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |