Obtaining quick and accurate diagnostic test results is vital for effective treatment of patients. Point-of-Care (POC) diagnostics function to decrease physician dependence on amply-equipped medical laboratories, thereby expediting the delivery and reducing costs of routine testing. While many POC diagnostics detect small molecules, specific detection and characterization of genomic material remains largely reliant upon enzymatic methods with extensive resource requirements for both assay interpretation and reagent support. The superior stability of nucleic acids to enzymes and the programmable nature of nucleic acid hybridization events make nucleic acids good candidates for the development of rugged and accurate POC diagnostics. Catalyzed hairpin assembly (CHA) is an enzyme-free nucleic acid signal amplification circuit that enables specific detection of oligonucleotides. In this work, we present the development of a modified version of CHA, herein referred to as split-catalyst CHA (scCHA), for discrimination of cancer-linked single-nucleotide polymorphisms in the human MDM2 gene and ricin-generated ribosomal apurinic sites.