HTAADVar

HTAADVar aggregates and automates clinical interpretation of genetic variants associated with heritable thoracic aortic aneurysm and dissection (HTAAD).

Key Features:

• Automated, disease- and gene-specific interpretation: Performs fully automated variant classification using disease- and gene-specific criteria and expert panel recommendations under the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) framework.
• Curated variant database: Maintains a curated database of 4,373 variants in HTAAD-related genes with metadata drawn from 697 publications and an in-house study of 790 patients.
• Automated pathogenicity assessment: Implements an interpretation engine that automatically assesses variant pathogenicity with reported sensitivity of 92.64% and specificity of 70.83%.
• Reported clinical diagnostic yield: Achieved a molecular diagnostic yield of 42.03% in a cohort of 790 patients.

Scientific Applications:

• HTAAD variant interpretation: Classification of disease-associated variants in HTAAD to support molecular diagnosis.
• Cohort and variant database analysis: Use in analyses of patient cohorts and aggregation of literature-derived variant metadata for HTAAD research.
• Extension to other genetic diseases: Framework applicable for adaptation to molecular diagnosis workflows of other hereditary genetic disorders.

Methodology:

Aggregates variants into a curated database and applies a fully automated interpretation engine that follows the ACMG/AMP framework using disease- and gene-specific criteria and expert panel recommendations to compute pathogenicity; performance was evaluated with reported sensitivity 92.64%, specificity 70.83%, and diagnostic yield 42.03% in 790 patients.