SIM1 and obesity due to melanocortin 4 receptor deficiency: Importantly, in all used gene panels at least the most important and well-known obesity-associated genes were tested, including among others LEP, LEPR, MC4R, POMC, PCSK1, ALMS1, GNAS, SH2B1, and SIM1. A strength of our diagnostic setting is that we followed the current ACMG guidelines for variant calling, leading to stringent selection of only pathogenic and likely pathogenic variants for which evidence from validated functional studies and from control populations has already been incorporated.