In the current research, two novel SOX5 variations, NM_006940.6: c.355C>T; p.(Gln119*) and NM_006940.6: c.640G>T; p.(Glu214*), were causally linked to AF as a prominent clinical manifestation of Lamb–Shaffer syndrome, therefore expanding the SOX5-related phenotypic spectrum. Here, SOX5 is linked to atrial fibrillation.