Project Grant R01HL183397

The National Heart, Lung, and Blood Institute awarded Geisinger Clinic $823,655 on August 17, 2026, under the Cardiovascular Diseases Research program (CFDA 93.837) to assemble and harmonize genomic and phenotypic data across three large biobanks—MyCode at Geisinger, BioVU, and the UK Biobank—approaching one million individuals to understand the disease spectrum and clinical modifiers of titin gene protein-truncating variants (TTNTV) in heritable cardiomyopathy.

TTNTV account for roughly 20 percent of familial and idiopathic dilated cardiomyopathy cases but are present in approximately 1 percent of the general population, creating uncertainty about disease risk in otherwise healthy carriers. The research tests how TTNTV variant type and location modulate penetrance of arrhythmias and cardiomyopathy to identify variants warranting close clinical management. The project investigates three hypotheses: differences in variant pathogenicity across the TTN gene, the spectrum of cardiac structure and function that remains clinically undetected, and the "two-hit" phenomenon where secondary factors such as chemotherapy and pregnancy influence disease development in TTNTV carriers. All three biobanks include cardiac imaging data—echocardiogram and cardiac MRI—for many participants.

Work is performed in Danville, Pennsylvania, with a period of performance from August 17, 2026, through May 31, 2031. The assistance type is a Project Grant.