Titin, the largest known protein in nature, is a giant sarcomeric protein that plays essential architectural, developmental, and regulatory roles in striated muscles. Mutations in the TTN gene (MIM: 188840) that encodes titin are related to a broad range of muscle diseases known as titinopathies, with diverse clinical manifestations including weakness, contractures, scoliosis, respiratory failure, and cardiomyopathy.1 In this case report, we describe two sisters with severe scoliosis, both carrying novel compound heterozygous variants in the TTN gene, yet presenting distinct clinical phenotypes, adding to the growing body of evidence linking TTN mutations to scoliosis and other titin-related disorders.