Evolutionary conservation, associated ADAMTS13 plasmatic activity, and age at first TTP episode requiring FFP of N- and C-terminal mutations of ADAMTS13. (A) Evolutionary conservation of amino acid residues affected by missense mutations of ADAMTS13 associated with congenital TTP in all cases reported in the literature. Conservation was estimated using SIFT. (B) Residual activity of ADAMTS13 and age at first TTP episode requiring FFP of patients with different C- and N-terminal mutations. Only mutations in homozygosis were considered.