Key result
Hydrophobicity-reducing missense variants destabilize titin domains and are specifically linked to DCM.
Why the study?
The underlying genetic defect in most dilated cardiomyopathy cases remains unknown, despite many patients carrying single titin missense variants of uncertain pathogenicity.
Comparison
Wild-type vs mutant p.C3575S titin domain I21
Design
Structural, molecular dynamics, and biochemical experimental study
Authors
Loading...
Titin I21 destabilization by C3575S may drive DCM; leaves open pathogenicity assessment for similar titin variants in patients.
Titin domain destabilization due to reduced core hydrophobicity is a mechanism causing dilated cardiomyopathy, providing a framework for assessing variant pathogenicity.
Martínez-Martín et al. (2023) studied Dilated cardiomyopathy. Hydrophobicity-reducing titin missense variants vs. Wild-type titin was evaluated on Protein destabilization and association with dilated cardiomyopathy. Hydrophobicity-reducing missense variants destabilize titin domains and are specifically associated with dilated cardiomyopathy.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: