Abstract
Holt–Oram syndrome is an autosomal dominant disorder characterized by congenital heart defects and distal upper‐limb abnormalities. Pathogenic variants in TBX5, located on chromosome 12q24.1, cause Holt–Oram syndrome. We report a 10‐year‐old boy with bilateral thumb anomalies, a large secundum atrial septal defect, and sinus bradycardia who was found to carry a maternally inherited TBX5 frameshift variant, c.130del; p.(Ala44ProfsTer22). This early truncating variant is predicted to cause loss of function through protein truncation or nonsense‐mediated decay. To the best of our knowledge, this specific variant has not previously been described in the peer‐reviewed literature. Detailed electrocardiographic and ambulatory rhythm findings further characterize the conduction phenotype associated with this variant.