Brett M. Kroncke

Kv11.1 (hERG) Protein Interaction Networks Connect Endocytic Trafficking to Polygenic Influences on Cardiac Repolarization

This study links polygenic scores for QT interval to changes in Kv11.1 protein interactions in hiPSC-CMs, revealing connections between genetic variants and endocytic trafficking mechanisms.

Damaging RBM20 E-rich domain variants are not rescued by gene replacement

The paper investigates E-rich domain variants of RBM20, showing they reduce protein abundance and cause splicing defects, but are not rescued by RBM20 overexpression.

Mapping the Functional Landscape of KCNQ1 to Define Ion Channel Mechanisms and Arrhythmia Risk

The paper maps the functional landscape of KCNQ1 variants to identify pathogenic and benign variants, revealing their impact on arrhythmia risk and ion channel mechanisms.

Patient-derived Cellular Models of Polygenic Scores: Application to Long QT Syndrome

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

Calibrated Functional Data Decreases Clinical Uncertainty for KCNH2-related 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.

Structural Evaluation of RYR2-CPVT Missense Variants and Continuous Bayesian Estimates of their Penetrance

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

EFP Analyzer: A fast, accurate, and easy-to-teach program for analyzing Extracellular Field Potentials from iPSC-derived cardiomyocytes

The paper introduces EFP-Analyzer, a software tool for analyzing extracellular field potentials from iPSC-derived cardiomyocytes, showing it accurately measures intervals and detects drug or mutation effects.

Generation of human induced pluripotent stem cell (hiPSC) lines from patients with extreme high and low polygenic scores for QT interval

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

Prognostic Value of Multiplexed Assays of Variant Effect and Automated Patch-clamping for KCNH2-LQTS Risk Stratification

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

Clinical interpretation of KCNH2 variants using a robust PS3/BS3 functional patch clamp assay

The paper establishes a functional patch clamp assay to classify KCNH2 variants in LQTS, using Z-scores to inform ACMG criteria and correlate with clinical scores.

Continuous Bayesian Variant Interpretation Accounts for Incomplete Penetrance among Mendelian Cardiac Channelopathies

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

A calibrated functional patch clamp assay to enhance clinical variant interpretation in KCNH2-related long QT syndrome

This study uses a high-throughput patch-clamp assay to reclassify KCNH2 variants of uncertain significance, providing evidence for clinical interpretation.

Arrhythmia variant associations and reclassifications in the eMERGE-III sequencing study

The paper identifies pathogenic variants in arrhythmia genes in eMERGE-III participants and reclassifies variants of uncertain significance using functional studies.

High-throughput reclassification of SCN5A variants

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

High-throughput discovery of trafficking-deficient variants in the cardiac potassium channel KCNH2

This paper introduces a high-throughput method to screen KCNH2 variants for trafficking defects, validating it with multiple assays and showing its utility for identifying loss-of-function variants.

Deep Mutational Scan of a cardiac sodium channel voltage sensor

The paper performs a deep mutational scan of SCN5A variants to assess their functional impact, identifying 40 gain and 33 loss of function variants with high accuracy.

A Bayesian method using sparse data to estimate penetrance of disease-associated genetic variants

The paper develops a Bayesian method to estimate penetrance of disease-associated variants using sparse data and applies it to SCN5A variants in Brugada syndrome.

A rare variant on a common risk haplotype of HFE causes increased risk of hereditary hemochromatosis

The paper identifies HFE E168Q as a novel pathogenic variant associated with hereditary hemochromatosis using Phenotype Risk Scores and validates its mechanism through experimental assays.