Abstract: Methods and systems for the detection of genetic mutations from a tissue sample (e.g., a preserved tissue sample) are provided. The method includes the steps of a) extracting a nucleic acid from a tissue or biological sample; b) preparing a targeted nucleic acid amplicon library from the extracted nucleic acid; c) sequencing the targeted nucleic acid amplicon library to produce tissue sample target nucleic acid sequence data; and d) analyzing the sample target nucleic acid sequence data to determine whether it contains a mutation (e.g., a mutation associated with a risk for a particular disease). The methods described herein advantageously can be performed in less than 36 hours.