Considering the rationale behind the ALFRED in silico method, we assessed the presence of somatic second hits (somatic variant or LOH) in available tumor samples from the carriers identified in our series (two tumors from NSD1 variant carriers and six tumors from KRT24 variant carriers), and from the 14 TCGA CRC patients with a damaging or predicting damaging variant in any of the five selected genes. The gene discussed is NSD1; the disease is neoplasm.