In silico studies of RET p.V262A. (A) Heat map representation of SNAP2 results depicting the likely impact of individual AA substitutions (y-axis) for each position (x-axis) on protein function. Substitutions with strong effects are depicted with dark red (score = 100), whereas weak substitutions are represented with blue (score = −100). White represents neutral substitutions. Black represents the corresponding wild-type residue. The V262 position is shown with yellow rectangles. (B) Comparative sequence analysis across representative phylogeny. The position of the variant is shown in blue box. Differences are highlighted in red. (C) 3D crystal structure of PDB 4ux8; p.V262A is marked with an arrow. (D) Thermodynamic change in Gibb's free energy caused by the p.V262A substitution as predicted by the mCSM.