A recent report illustrates the power of combining recent technological advances to define important, organ-specific phenotypes of previously refractory proteins. Genetic variants in the protein titin have been understudied due to the difficulties in handling enormous sequences and the cognate protein. But the giant protein is beginning to yield its secrets with the advent of Nex-Gen sequencing, our developing ability to create stable cardiomyocytes from patient-derived induced pluripotent stem cells, and the creation of three-dimensional microtissues capable of recapitulating the stress, strain and contractile properties of a myofibril. The ability to accurately model a patient’s pathology in isolated systems holds the promise of translating laboratory findings into effective, prospective surveillance and even therapy.