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Genome-wide association studies have identified genetic variants including rs13143308T in the homeobox gene Pitx2 associated with atrial fibrillation (AF) populations. However, the molecular mechanisms leading to AF due to the rs13143308T variant are poorly understood. Therefore, this study aims to investigate the effects of this variant-induced alteration in calcium handling on properties of Ca2+-transients (CaT) and spontaneous calcium-release events (SCaEs). Based on recent experimental data on variants-induced alterations in ryanodi