Abstract: Integrated short read and long read sequencing for genomic variant detection is described. A coverage modulation engine selects a short read sequencing coverage and a long read sequencing coverage for a nucleic acid sequencing event based on a sequencing target of the nucleic acid sequencing event and at least one constraint. A sequencing protocol generator determines a short read sequencing protocol based on the selected short read sequencing coverage and determines a long read sequencing protocol based on the selected long read sequencing coverage. An integrated variant calling module outputs a variant call based on short read sequencing data generated via the short read sequencing protocol and long read sequencing data generated via the long read sequencing protocol.