Congenital myopathies are a heterogeneous collection of disorders defined by neonatal muscle weakness, or hypotonia, and many myopathies can progress to extreme conditions in which patients require clinical interventions for proper respiration and mobility. Over 23 distinct heterozygous mutations in Tropomyosin 2 (TPM2) have been identified in patients with Nemaline Myopathy (NM), yet the mechanisms by which these mutations contribute to the disease phenotype remain largely unknown. The current clinical hypothesis is that TPM2 NM alleles are gain-of-function mutations that disrupt sarcomere contractility in otherwise normal muscle. Based on our previous developmental studies, we hypothesized that TPM2 NM alleles also disrupt multiple aspects of myogenesis prior to sarcomere assembly. We expressed 9 human TPM2 NM alleles in Drosophila embryonic body wall muscles and assayed muscle development. Each TPM2 NM allele disrupted myogenesis, and multiple alleles caused myotubes to attach to the wrong tendon or to no tendon at all. These results strongly support our hypothesis that the NM disease etiology is due in part to defects in myogenesis. This is the first study to systematically characterize TPM2 NM alleles in an in vivo system, and highlights the utility of using Drosophila genetics to functionally annotate human disease alleles. Our studies will also be a foundation for studying TPM2 NM alleles during mammalian myogenesis.