Patients with thrombocytosis or erythrocytosis who are investigated for a myeloproliferative neoplasm (MPN) often undergo next generation sequencing-based testing, either on a limited panel (e.g. JAK2, CALR, MPL) and/or on a broader panel of “myeloid” genes.

Most patients who have an MPN are found to have recurrent variants at mutational hotspots in JAK2, CALR or MPL, which are known to drive disease. However a small minority of patients are found to have uncommon acquired or germline variants in MPN driver genes, or pathogenic variants in other myeloid genes.

These can be of uncertain relevance to the myeloproliferative phenotype and to the risk of complications such as thrombosis.

Accurate interpretation of the pathogenic significance and clinical implications of these variants may be challenging. However this is aided by knowledge of recurrence in other patients with a relevant phenotype.