Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000697091 | SCV000825682 | uncertain significance | Charcot-Marie-Tooth disease, dominant intermediate F | 2018-03-14 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with alanine at codon 303 of the GNB4 protein (p.Asp303Ala). The aspartic acid residue is weakly conserved and there is a moderate physicochemical difference between aspartic acid and alanine. This variant is present in population databases (rs751851667, ExAC 0.002%). This variant has not been reported in the literature in individuals with GNB4-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. |