Objective: To explore the etiology of a typical case of unexplained sudden death in Yunnan (referred to as “Yunnan sudden death”), correlate genotypes with phenotypes to identify high-risk populations, and provide a basis for intervention measures. Methods: Epidemiological and clinical investigation data, as well as blood biochemical test results, were collected from three cases of Yunnan sudden death. Whole exome sequencing (WES) was performed on blood samples, using GRCh38/HG19 as the reference sequence. Mutation sites were screened based on genetic heart disease-related gene variants and subjected to filtering, annotation, and analysis. Protein function prediction analysis of mutated genes was conducted using SIFT, Mutation Taster, and PolyPhen2 software. Results: After screening, harmful and ambiguous mutation sites were retained, involving 18 mutation site information from four genetic heart disease-related genes (DMD, SIDT1, CSRP3, DSG2). Among them, 17 were predicted by software to have harmful, harmful, or pathogenic protein functions. Deceased 2 carried six mutation sites in DMD, deceased 2 and deceased 4 jointly carried nine mutation sites in SIDT1, and deceased 3 carried two mutation sites in CSRP3. Conclusion: The causes of death in the three cases of Yunnan sudden death in this study are highly likely related to mutations in genetic heart disease-related genes.