Background Robust data regarding genotype-phenotype correlations in left ventricular noncompaction cardiomyopathy (LVNC) are lacking. Methods About 72 cardiomyopathy-related genes were comprehensively screened in a cohort of LVNC patients using targeted sequencing. Baseline and follow-up data were collected. The primary endpoint was a composite of death and heart transplantation. Results A total of 83 unrelated adult patients were included in analyses. Following stringent classification according to the American College of Medical Genetics and Genomics (ACMG) guidelines, 36 pathogenic variants of 14 genes were detected in 32 patients. Among them, 12 patients carried at least one nonsarcomere variant (NSV). At baseline, NSV carriers had a higher frequency of atrial fibrillation, but lower left ventricular ejection fraction, than did noncarriers. During a median follow-up of 4.2 years, NSV carriers experienced a higher rate of the primary endpoint compared with noncarriers. There was no significant difference in the rate between carriers of sarcomere variant (SV) and noncarriers, as well as between carriers of SV and NSV. The presence of NSV was associated with an increased risk of the primary endpoint independent of age, sex, and cardiac function (hazard ratio: 3.61, 95% confidence interval: 1.42-9.19, p = .002). Conclusion NSV may act as a genetic modifier and worsen the clinical phenotype in patients with LVNC.