ID: 4349375 DECODING THE STRUCTURAL CARDIOGENOMICS OF NAV1.5: INTEGRATING ALPHAFOLD STRUCTURAL CONTEXT AND PMUT PATHOGENICITY SCORES TO PRIORITIZE SCN5A MISSENSE VARIANTS

Variant interpretation in SCN5A, the gene encoding the cardiac sodium channel Nav1.5, is critical for diagnosing Brugada and long QT syndromes. Most SCN5A missense variants remain “uncertain” because functional patch-clamp assays are slow and sequence-based predictors yield many false positives. Adding AlphaFold’s 3-D context may sharpen pathogenicity calls but has not been systematically tested.