High-throughput biophysical characterization of cardiac myosin-binding protein C missense variants
Active Project Grant Awarded Last action
- Award ID
- F31HL186627
- Recipient
-
Northwestern University UEI KG76WYENL5K1
- Awarding agency
-
National Heart Lung and Blood Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $45,327
Award facts
- Assistance listing
- 93.837 Cardiovascular Diseases Research
- Completion date 0% complete
- Place of performance
- Chicago, IL 60611, USA
Award details come from USAspending.gov.
Description
- Abstract
- Hypertrophic cardiomyopathy (HCM) affects approximately 1 in 500 individuals and is a leading cause of sudden cardiac death in young people. Mutations in the cardiac myosin-binding protein C (CMYBP-C) represent the most frequent genetic cause of HCM. Despite the clinical importance, over 90% of missense variants in CMYBP-C's folded domains remain unclassified or of uncertain significance, hindering genetic risk stratification and clinical decision-making strategies. Understanding how these missense variants affect CMYBP-C's biophysical properties will improve variant classification. However, the relatively large size and extensive mutational landscape of CMYBP-C make IT challenging to evaluate each variant's biophysical properties using traditional assays. This project proposes to apply high-throughput experimental assays to measure key properties essential for CMYBP-C's function, folding stability and myosin binding, across all missense variants in CMYBP-C. Using cdna display technology, I will quantify folding stability and myosin binding for over 22,000 missense variants in the immunoglobulin-like and fibronectin domains of CMYBP-C, including 41 clinvar- annotated variants. Correlating these biophysical properties with clinical phenotypes of known annotated variants will strengthen our understanding of the association between folding stability, myosin binding, and variant pathogenicity. The resulting high-throughput datasets will provide valuable insights to inform the risk stratification of current and future missense variants.
Quick answers
Who received award F31HL186627?
F31HL186627 was awarded to Northwestern University by National Heart Lung and Blood Institute (National Institutes of Health) on December 1, 2026.
How much is award F31HL186627 worth?
$45,327 has been obligated on F31HL186627.
On GovTribe
See this award's full record
- Every transaction and subaward
- The recipient's other awards and teaming partners
- Similar grant awards
- Ask GovTribe AI about this award