Complementary computational and experimental evaluation of missense variants in the ROMK potassium channel
Fig 3
Scatter plots comparing computational predictions and identifying consensus and discordant data.
The two scatter plots compare the predictions from Rhapsody and EVmutation (left) and those from Rhapsody and PolyPhen-2 (right), allowing the outputs to be grouped in three different categories: consensus neutral, consensus deleterious, and discordant, as indicated by the labels. Cutoff values between neutral/deleterious predictions for each method are represented by dashed lines. Note that EVmutation’s ΔE score anticorrelates with the expected pathogenicity of variants. The 31 variants selected for experimental validation and two controls (see text, Fig 5 and S1 Table) are labelled in the two plots and marked by different symbols and colors based on the experimentally observed phenotypes. Results for those variants which cannot be evaluated using EVmutation, due to the absence of a suitable Pfam domain and/or MSA, are shown in the right plot only, with abscissa values based on PolyPhen-2 scores. Labels written in square brackets refer to rat ROMK1 variants that were experimentally tested after substituting for the counterparts in the human sequence.