We found evidence that SETD2-associated NDD may be associated with tumor susceptibility and, though we did not identify a clear methylation episignature for SETD1A-NDD, for SETD2-associated NDDs we identified methylation alterations that correlated with the clinical heterogeneity of SETD2 codon 1740 and non-codon 1740 LoF mutations. This evidence concerns the gene SETD2 and neoplasm.