Would an MPL variant mutation of unknown clinical significance be considered diagnostic of essential thrombocytosis in a patient with longstanding elevation in the platelet count, and for whom all secondary causes have been excluded?

A bone marrow biopsy should be performed if not already done to complete diagnostic work-up for an MPN. If the MPL variant is truly of unknown significance, then that alone is not diagnostic of an MPN. The WHO 5th edition criteria for ET diagnosis are summarized in Loghavi et al., PMID 38043791 and ...