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Heres the key signal: - Molecular diagnosis achieved in 14% of cases - 78% had at least one reportable variant - 37% of diagnosed cases carried variants linked to hematologic malignancy Whats changing under the hood: - Broad gene coverage (67 platelet-related genes) enables detection beyond classical phenotypes - High burden of VUS (major diagnostic bottleneck) - Functional testing alone misses milder or complex platelet defects - Genetic findings frequently extend beyond platelets systemic disease risk Clinical insight: - Most diagnoses clustered in thrombocytopenia-associated genes - Common hits: ANKRD26, ETV6, ACTN1 - Key overlap with malignancy predisposition genes: RUNX1, ETV6, ANKRD26 Big questions for the field: Should NGS move earlier in the diagnostic algorithm

& Sadar, M