Left: all 3,477 ClinVar variants with highly variable ESM1b effect scores across different isoforms (defined by s.d. > 2). Center: the lowest and highest isoform scores predicted for all VUS from the left panel (top two boxes), compared to the mean scores (across isoforms) of VUS, benign or pathogenic variants (as in Fig. 2d ; bottom three boxes). The boxes represent the Q1Q3 range and median (Q2) line; whiskers correspond to 1.5 IQR; outliers (outside the whiskers) are shown individually. Right: the distribution of the lowest and highest isoform scores predicted for all VUS from the left panel, compared to the distributions for pathogenic or benign variants from ClinVar, HGMD and gnomAD (as in Fig. 2a ). Across all panels, the number of variants associated with each category is shown in parentheses.
