Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001045682 | SCV001209551 | uncertain significance | Charcot-Marie-Tooth disease dominant intermediate F | 2023-08-04 | 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. 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 GNB4 protein function. ClinVar contains an entry for this variant (Variation ID: 843131). This variant has not been reported in the literature in individuals affected with GNB4-related conditions. This variant is present in population databases (rs769949519, gnomAD 0.009%). This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 164 of the GNB4 protein (p.Thr164Lys). |