Reaching even the highest allele frequencies in genes such as NKX2-5, NOTCH1 and PTPN11, and some were reclassified as pathogenic according to in silico prediction tools, suggesting the need for further studies on the impact and frequency of these variants in the population with congenital heart disease to allow the reach of precision medicine. This evidence concerns the gene NKX2-5 and congenital heart disease.