We found that genes down-regulated in mutant organoids were associated with striated muscle differentiation, while mutant up-regulated genes were often related to energy and metabolism, which provided the first (in vitro) characterization of molecular effects of the NKX2-5 c.673 C > A mutation and may constitute a first step towards more detailed models of the contribution of this genetic lesion towards Ebstein’s anomaly. The gene discussed is NKX2-5; the disease is Ebstein anomaly.