Matthew J. O’Neill

The paper develops a multidimensional assay to assess variant effects in MYBPC3, reclassifying variants and uncovering disease mechanisms in hypertrophic cardiomyopathy.

This study identifies rare and low-frequency non-coding variants at the SCN5A locus associated with Brugada syndrome using whole-genome sequencing and functional assays.

The paper uses automated patch clamp data to reclassify SCN5A variants in Brugada Syndrome, improving variant classification and penetrance stratification.

The paper uses patient-derived iPSC-CMs to show that polygenic scores influence cardiac electrophysiology and drug response in Long QT Syndrome.

The paper presents a method to reduce clinical uncertainty in KCNH2-related long QT syndrome by using calibrated functional data to classify variants of uncertain significance.

The paper evaluates RYR2-CPVT missense variants using Bayesian penetrance analysis and finds it outperforms existing tools.

The paper generates hiPSC lines from patients with extreme polygenic scores for QT interval to study LQTS genetic and cellular complexity.

This paper introduces ParSE-seq, a multiplexed assay to assess splice-altering variants, showing high correlation between experimental and computational predictions.

This paper evaluates how functional variant data and penetrance estimates improve risk stratification for LQTS in KCNH2 missense variant carriers.

The paper validates an in vitro SCN5A Brugada Syndrome assay to reclassify variants of uncertain significance as pathogenic or benign.

The paper identifies a novel SCN5A variant, E171Q, that creates a gating pore current by neutralizing a negative charge in the S2 helix, leading to MEPPC and altered voltage dependence.

The paper develops Bayesian models to estimate variant penetrance in Mendelian cardiac channelopathies, revealing continuous penetrance distributions and structural insights.

The paper uses functional assays to reclassify splice-altering variants in Brugada Syndrome and Long QT Syndrome genes, identifying pathogenic and benign classifications.

The paper shows that most SCN5A missense loss-of-function variants cause dominant negative effects and are associated with higher Brugada Syndrome risk.

This study reclassifies SCN5A variants using high-throughput patch clamping, finding most variants of uncertain significance are either benign or pathogenic.