Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000688385 | SCV000815995 | uncertain significance | Charcot-Marie-Tooth disease, X-linked dominant, 6 | 2018-09-25 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with threonine at codon 376 of the PDK3 protein (p.Ala376Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs781166988, ExAC 0.01%). This variant has not been reported in the literature in individuals with PDK3-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: "Deleterious"; 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. |