ADAMTS13 sSNVs affect the folding energy and mRNA secondary structure. (A) Stacked column plot that displays the proportions of all sSNVs in each exon that decrease ΔΔG (–, blue), increase ΔΔG (+, red), or do not change ΔΔG (0, white) based on average value obtained from all 4 algorithms (see Methods). (B) Stacked column plot that displays the ratio of significantly different sSNVs (P values < .05) in each exon. (C) Synonymous ADAMTS13 variants with significantly (*) different ΔΔG compared with WT as predicted by at least one algorithm (P < .05). (D) Optimal full-length mRNA secondary structure of ADAMTS13 predicted by RNAFold for variants 999G>A and 1462C>A compared with WT ADAMTS13. (E) Correlation between the ΔΔG values obtained by mFold, remuRNA, KineFold, and NUPAC for all 376 ADAMTS13 sSNVs. Differences considered significant in which P < .05 (see supplemental Methods for description of P value computation and supplemental Excel File 1 for P values).