Inherited retinal diseases (IRD) comprise a heterogeneous set of clinical and genetic disorders that lead to blindness. Given the emerging opportunities in precision medicine and gene thera-py, it has become increasingly important to determine whether DNA variants with uncertain significance (VUS) are responsible for the patients’ IRD. This research was performed to assess the functional consequence of six VUS identified in patients with IRD. Clinical assessments in-cluded an ophthalmic examination, best corrected visual acuity, and kinetic perimetry. Imaging was acquired with the Optos ultra-widefield camera and spectral-domain optical coherence to-mography (SD-OCT). Genetic testing was performed by Molecular Vision Laboratories. VUS that were predicted to alter splicing were analyzed with a minigene assay which revealed that VUS in the genes OPA1, CNGB1, and CLUAP1 altered spicing mechanisms. Due to the emerging gene and cell therapies, these results expand the genotype-phenotype correlations for patients diag-nosed with an IRD.