Genome sequencing of 865 index cases with bleeding and platelet disorders of unknown molecular etiology revealed 2 pedigrees with a premature stop codon in TPM4. This variant was absent from nearly 75,000 control DNA samples and segregated with large platelets and concomitant low platelet count (a phenotype termed macrothrombocytopenia) in the 2 pedigrees. The gene discussed is TPM4; the disease is blood platelet disease.