The effects of two SCN5A mutations (Y1795C, Y1795H), previously identified in one LQT3 and one BrS families, were investigated by means of numerical modeling of ventricular action potential (AP). A Markov model capable of reproducing wild type as well as mutant I_Na was identified and was included into the Luo-Rudy ventricular cell model for AP simulation. The characteristics of endocardial, midmyocardial and epicardial cells were reproduced by differentiating I_To and the ratio of I_Ks / I_Kr. Administration of Flecainide and Mexiletine was simulated by appropriately modifying I_Na, I_Ca, I_To and I_Kr. Y1795C prolonged AP in a rate dependent manner and early afterdepolarizations (EADs) appeared during bradycardia in epicardial and midmyocardial cells; Flecainide and Mexiletine shortened AP and abolished EADs. Y1795H resulted in minimal changes in the APs; Flecainide but not Mexiletine induced APs heterogeneity across the ventricular wall that accounts for the ST segment elevation induced by Flecainide in Y1795H carriers. The AP abnormalities induced by Y1795H and Y1795C can explain the clinically observed surface ECG phenotype. For the first time by modeling the effects of Flecainide and Mexiletine we are able to gather mechanistic insights on the response to drugs administration observed in affected patients.