An atrial septal defect (ASD) is an opening in the wall between the atria, the upper two chambers of the heart. Each year, approximately 4 of every 10,000 infants born in the United States is born with an ASD, comprising 6% to 10% of all cases of congenital heart disease. Many ASDs resolve spontaneously but in some cases they remain open, resulting in disordered blood flow. Untreated, these defects are associated with a broad range of symptoms, including shortness of breath, heart palpitations, infective endocarditis, swelling of the extremities, heart failure, and stroke. Treatment of ASD is symptom-driven and may include observation, medications, and surgery. Many ASDs occur sporadically and can result from environmental influences during gestation, such as maternal drug use or Rubella infection. ASDs are also associated with syndromic conditions such as trisomy 13 (Patau syndrome), trisomy 21 (Down's syndrome) and Holt-Oram syndrome. Atrioventricular (AV) block is an electrical conduction disorder that is sometimes associated with ASD. AV block ranges in severity from asymptomatic cases to more serious cases that require pacemaker insertion. The nucleotide kinase (NK) transcription factor related, locus 5 (Drosophila) (NKX2-5) gene (also known as the CSX gene) is located on the long arm of chromosome 5 at band q34. NKX2-5 encodes a homeodomain-containing transcription factor essential to cardiac development and the maintenance of cardiac electrical function. NKX2-5 variants are associated with a variety of congenital heart defects, including ASD, AV block, tricuspid valve abnormality, reduced left ventricular function, ventricular septal defect (VSD), Ebstein's abnormality, tetralogy of Fallot (TOF), arrhythmia, and hypoplastic left heart syndrome (HLHS). This report will focus on the connection between NKX2-5 variants and ASD and AV block.