In summary, our data show that the rare T1D-protective E627* and I923V variants cause loss of MDA5-dependent IFN-β signaling, in agreement with previous studies, whereas the protective R843H and T946A variants had no significant effect on EMCV-induced signaling in the combination commonly found in human subjects (H843/A946). The gene discussed is IFNB1; the disease is type 1 diabetes mellitus.