Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000651047 | SCV000772896 | uncertain significance | Cowden syndrome 6 | 2017-10-04 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with threonine at codon 147 of the AKT1 protein (p.Met147Thr). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and threonine. This variant is present in population databases (rs758456890, ExAC 0.02%). This variant has not been reported in the literature in individuals with AKT1-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 C25"). 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. |