Figure 4.

Prioritizing variants of uncertain significance (VUSs) from thermodynamic data and CADD scores. Folding free energy differences (ΔΔG_Fold) versus CADD score for all missense variants observed in the Deafness Variation Database (DVD) with points colored according to DVD classification (panels a and c) or model confidence at the variant’s amino acid position (panel b). CADD score and ΔΔG_Fold show a positive correlation. A high ΔΔG_Fold and high CADD score in confident regions of a protein model favor pathogenic variants; low ΔΔG_Fold and low CADD score favor benign variants and exhibit greater variety in model confidence. Prioritized VUSs have both high ΔΔG_Fold and high CADD scores