A targeted sequencing assay for 49 genes and gene hotspots that are recurrently mutated in myeloid neoplasms, such as MDS and AML. This assay is intended to be used for both initial diagnosis and measurable/minimal residual disease (MRD) monitoring. MyeloSeq-HD uses a high coverage (12Gbases) unique molecular identifiers (UMIs)-based error corrected sequencing approach to achieve >95% sensitivity for previously identified mutations with VAFs ≥0.25%; sensitivity for newly detected variants is limited to 2% VAF. For post allogeneic hematopoietic stem cell transplant patients, MyeloSeq-HD can detect mixed chimerism.