In silico based analysis of the impact of HDGC-associated E-cadherin missense mutations.

Only mutations that localize in the domains covered by the structural models are listed. FoldX calculations are reflected by the value of native-state stability changes (ΔΔG = ΔGWT−ΔGMut), expressed in kcal/mol. Mutations associated to structural impact present ΔΔG>0,8 kcal/mol in the FoldX column, and values below 0,05 in the SIFT column are considered to be intolerant due to high conservation. Predictions were scored as: True Positive (TP) when the software predicts high impact and the mutants exhibits in vitro loss of function; True Negative (TN) when the software predicts no impact and the mutant is functional in vitro; False Positive (FP) when the software predicts high impact but the mutant is functional in vitro; and False Negative (FN) when the software predicts no impact and the mutant exhibits in vitro loss of function. Only mutations that have been functionally characterized in vitro are classified. The mutations that have been described to impact the splicing pattern are depicted with (a). Mutations found at a frequency higher than 1% in one control population are considered polymorphisms, and marked with (b). Mutations published as personal communications are referenced with (c). The newly identified mutations are listed in the bottom of the table, unpublished are marked with a (d). ND – Not Determined.