Cardiomyopathies and cardiac arrhythmias represent a heterogeneous group of pathologies. If not diagnosed promptly, they can lead to serious complications such as heart failure, stroke, or sudden death. The role of medical genetics laboratories in identifying the gene mutation responsible for these heart defects is becoming increasingly significant. Identifying these diseases in the pre-clinical stage allows preventive and therapeutic strategies to be implemented which, in some cases, can save patients’ lives. In this article, we report the case of a 64-year-old Caucasian male patient with a novel “no-start” variant NM_012259: c.-29_12del p.(?) in the Hairy Enhancer-of-split YRPW-related motif 2 (HEY2) gene, located on the long arm of chromosome 6 (6q22.31). This variant has never been described in the literature. According to the American College of Medical Genetics and Genomics (ACMG) classification, this variant is classified as probably pathogenic (class IV, PVS1, PM2).The deletion observed includes the loss of 31 nucleotides falling within the 5’ untranslated region (5’UTR) and 10 nucleotides falling within the Upstream Open Reading Frames region (nt: ATGAAGCGCC) (uORFs). The patient with the variant found in the HEY2 gene presents hypokinetic dilated cardiomyopathy (ejection fraction 40-45%) and massive ventricular/ supraventricular arrhythmias (18,000 ventricular ectopic beats/24h), with a complex clinical picture characterized by aortic dilatation (47 mm), diffuse hypokinesia of the left ventricle and cardiac rhythm instability.