Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics | RCV000516785 | SCV000613487 | likely pathogenic | not provided | 2020-02-18 | criteria provided, single submitter | clinical testing | Not found in the total gnomAD dataset, and the data is high quality. Found in at least one patient with expected phenotype for this gene. Predicted to have a damaging effect on the protein. Inconclusive segregation with disease. Variant is in an important domain. |
| Labcorp Genetics |
RCV000544254 | SCV000658913 | pathogenic | Charcot-Marie-Tooth Neuropathy X | 2023-11-24 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 160 of the GJB1 protein (p.Tyr160His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Charcot-Marie-Tooth disease (CMT) (PMID: 9361298, 18379723, 19691535). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 447432). 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 not expected to disrupt GJB1 protein function with a negative predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV000516785 | SCV002574194 | likely pathogenic | not provided | 2022-03-15 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in an individual with Charcot-Marie-Tooth disease (Keckarevic-Markovic et al., 2009); This variant is associated with the following publications: (PMID: 21291455, 9361298, 18379723, 19691535) |
| Inherited Neuropathy Consortium | RCV000789189 | SCV000928541 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |