SETBP1 and Schinzel-Giedion syndrome: In contrast to loss-of-function (LoF) variant leading to SETBP1 haploinsufficiency disease (SETBP1-HD), characterized by hypotonia and mild motor developmental delay/intellectual disability (MIM: #616,078), known SETBP1 variants causing SGS are gain-of-function (GoF) and located within a 12 bp hotspot region encoding SETBP1 amino acid residues 868–871, which are associated with the canonical SGS phenotype.