Continuous Bayesian variant interpretation accounts for incomplete penetrance among Mendelian cardiac channelopathies.

ABSTRACT:

Purpose

The congenital Long QT Syndrome (LQTS) and Brugada Syndrome (BrS) are Mendelian autosomal dominant diseases that frequently precipitate fatal cardiac arrhythmias. Incomplete penetrance is a barrier to clinical management of heterozygotes harboring variants in the major implicated disease genes KCNQ1, KCNH2, and SCN5A. We apply and evaluate a Bayesian penetrance estimation strategy that accounts for this phenomenon.

Methods

We generated Bayesian penetrance models for KCNQ1-LQT1 and SCN5A-LQT3 using variant-specific features and clinical data from the literature, international arrhythmia genetic centers, and population controls. We analyzed the distribution of posterior penetrance estimates across 4 genotype-phenotype relationships and compared continuous estimates wit

SUBMITTER: O'Neill MJ 

PROVIDER: S-EPMC9992222 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature