Fig. 1

Schematic representation of IQSEC2 isoforms and location of pathogenic IQSEC2 variants on the longest isoform. (a) Schematic representation of the three IQSEC2 isoforms resulting from alternative promoter usage (P1 vs. P2) and splicing. Blue/gray boxes respectively indicate exons present/absent in the longest isoform. The pink star indicates the location of the IQSEC2 variant (unknown significance) identified in patient 47. (b) Location of IQSEC2 pathogenic variants reported in this study (above) or in the literature (below) on the schematic representation of the longest NM_001111125.2 isoform (numbered blue boxes correspond to exons) and corresponding protein domains: N-terminal coiled coil (CC) domain, IQ calmodulin-binding motif (IQ), SEC7 and Pleckstrin homology (PH) domains, and PDZ-binding motif (STVV). Square: predicted truncating variants; circle: missense variants; triangle: in-frame deletion; bow tie: splice variants; pink: variants present in affected females; blue: variants present in affected males; yellow: variants present in affected males and females. Red dot: de novo occurrence; green dot: maternal inheritance; orange dot: suspected gonadal mosaicism. No dot indicates inheritance is unknown. Horizontal lines indicate the extent of large deletions on the corresponding coding sequence. Variants underlined: previously published without clinical data and included in this study. Variants of unknown significance (VUS) or variants from the literature for which sex was unknown are not indicated on this schematic