Extended Data Fig. 2: Variant effect predictor (VEP) correlations to laboratory-tested GIPR variants.
a, Cluster heatmap of the VEP normalized predicted deleteriousness scores, ranging from benign (0) to deleterious (1). The x-axis shows the included VEPs, and the classification of the laboratory-tested variants according to cyclic adenosine monophosphate (cAMP) accumulation (left). b, Prediction of variants potentially leading to a loss-of-signalling (LoS) molecular phenotype with four VEP masks (M1–M4)15. The 47 GIPR variants and their allele frequencies in the Danish population (all four study cohorts combined) are shown in the left panel, sorted according to their cAMP production (from low (bottom) to high (top)) compared with that of WT (Fig. 1d). M1, the Loss-of-Function Transcript Effect Estimator (LOFTEE) high-confidence (HC) mask with predicted LoS variants (red). M2–M4, grouped VEPs. A variant was considered a LoS variant if all VEPs in one of the four masks predicted the variant as a LoS variant (red). ‘pLoS’ represents the variants predicted to have a LoS molecular phenotype (bright red). ‘in vitro LoF’ represents the tested GIPR LoF variants with < 50% cAMP production (bright red). NAs are white. In total, 17 variants were pLoS variants, of which 15 overlapped with the in vitro cAMP LoF variants, and two were in vitro cAMP WT-like variants.
