Our study was not specifically designed to address whether the NOD2 variant was the causal or risk factor of disease in our patient, but the distinct location of the variant triggered assessment of NOD2-mediated signaling and interacting networks, since previously reported CD-associated NOD2 variants are mainly localized in or near the LRR domain (Fig. 1A)14–16. The gene discussed is NOD2; the disease is Cowden disease.