Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics | RCV002474290 | SCV002770770 | pathogenic | not provided | 2021-06-15 | criteria provided, single submitter | clinical testing | This variant is statistically more frequent in affected individuals than in the general population and/or healthy controls. Assessment of experimental evidence suggests this variant results in abnormal protein function. Multiple studies in various cell types show that this variant prevents cell-to-cell junctions from functioning (PMID: 17146396, 26749107). |
| Labcorp Genetics |
RCV002474290 | SCV004295455 | uncertain significance | not provided | 2023-07-20 | criteria provided, single submitter | clinical testing | 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. Experimental studies have shown that this missense change affects GJB2 function (PMID: 17146396, 26749107). 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 GJB2 protein function. ClinVar contains an entry for this variant (Variation ID: 1806861). This missense change has been observed in individual(s) with clinical features of GJB2-related conditions (PMID: 11102979, 17666888, 19366456, 20234132, 21366436, 25493717). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 47 of the GJB2 protein (p.Glu47Lys). |