The Short QT syndrome (SQTS) is associated with ventricular fibrillation and sudden cardiac death. One of its variants, SQT1 is linked to a gain-in-function mutation (N588K) of the human-ether-à-go-go-related-gene (hERG) potassium channel which encodes the rapid-delayed rectifier K+ current (IKr)1. In this study, a mathematical model was developed that quantifies the functional impact of the mutation on ventricular cell electrical action potentials. A Markov chain model of IhERG2 was modified to incorporate the experimentally observed kinetic properties of wild type (WT) and N588K-mutated hERG (N588K-hERG). These kinetic properties include (1) the profound (60-100) mV positive shift in the voltage dependence of inactivation of N588K-hERG; (2) the substantial increase of IhERG early during the ventricular action potential (AP) waveform; (3) the generation of rapid, transient, outward currents in response to premature, depolarising stimuli under ‘paired stimuli’ experiments1, 3. To reproduce the experimentally observed kinetic properties with the Markov chain model for both WT and the mutation, the Levenberg-Marquardt algorithm (LMA) in combination with the Broyden-Fletcher-Goldfarb-Shanno (BFGS) method4 were used to minimise the residual between the AP clamp IhERG experimental data and the simulated AP clamp result and to obtain the parameters that faithfully reproduced the experimental AP Clamp kinetics. The resulting formulation was then further validated by comparing simulated results from different voltage clamp protocols – for activation, inactivation and deactivation – against the experimentally observed results. The validated IKr model was then incorporated into the ventricular cell model developed by ten Tusscher et al5. The resulting model was then used to perform simulations of ventricular action potentials (APs) and IKr current. At a simulation rate of 1Hz, endocardial (ENDO) action potential duration (APD90) was shortened from 321 ms for WT to 212 ms for N588K-hERG, epicardial (EPI) APD90 was shortened from 313 ms to 196 ms and mid-myocardial (MID) APD90 from 438 ms to 233 ms. This simulation study further substantiates the causative link between altered IKr kinetics arising from the N588K mutation and ventricular APD shortening, and provides models that can further be used to investigate the cell- and tissue- substrates for arrhythmia in SQT1.