Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000643971 | SCV000765658 | uncertain significance | Charcot-Marie-Tooth disease, type 4A | 2019-06-28 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with threonine at codon 87 of the GDAP1 protein (p.Ile87Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs751297226, ExAC 0.001%). This variant has not been reported in the literature in individuals with GDAP1-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 C65"). 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. |