Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000654848 | SCV000776750 | uncertain significance | Charcot-Marie-Tooth Neuropathy X | 2023-10-29 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 187 of the GJB1 protein (p.Lys187Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 9361298). ClinVar contains an entry for this variant (Variation ID: 543925). 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 with a positive predictive value of 80%. 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. |
Mendelics | RCV002248849 | SCV002517136 | uncertain significance | not specified | 2022-05-04 | criteria provided, single submitter | clinical testing | |
Athena Diagnostics Inc | RCV003482294 | SCV004229562 | likely pathogenic | not provided | 2023-03-07 | criteria provided, single submitter | clinical testing | This variant has been identified in at least one individual with clinical features associated with this gene. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Computational tools predict that this variant is damaging. The variant is located in a region that is considered important for protein function and/or structure. |
Inherited Neuropathy Consortium | RCV000789818 | SCV000929202 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |