Background/Objectives: Obesity poses a major public 48 health concern. Although BMI heritability is estimated at 49 40-80%, genetic diagnostics remain challenging. 50 This study aims to (i) assess the diagnostic yield of 51 monogenic obesity in a large patient sample using 52 exome-wide data, (ii) identify predictors to improve 53 genetic testing criteria, and (iii) evaluate whether the 54 identified genes are included in public obesity gene 55 panels. 56 Subjects/Methods: We reviewed the genetic test results 57 of 521 patients with obesity. 84.7% underwent whole58 exome analysis, 15.3% were analyzed using a multi59 thousand gene panel. 60 Results: Monogenic obesity was diagnosed in 5.8% of 61 patients, while 7.1% carried a potentially obesogenic 62 variant. Diagnostic yield was higher in children (6.3%) 63 and patients with syndromic obesity (7.0%). Surprisingly, 64 diagnostic yield was lower in severe obesity cases. 40% 65 of patients with monogenic obesity carried variants in 66 genes not included in current obesity panels. 67 Conclusion: Overall, 12.9% of patients had monogenic 68 obesity or a potentially obesogenic variant. These findings suggest that genetic testing should not be limited 70 to patients with extreme obesity. Current obesity panels 71 miss crucial syndromic genes, demonstrating a need for 72 more comprehensive panels and the superiority of whole 73 exome sequencing in obesity.