Enhanced Classification of Brugada Syndrome-Associated and Long-QT Syndrome-Associated Genetic Variants in the SCN5A-Encoded Na(v)1.5 Cardiac Sodium Channel.

ABSTRACT:

Background

A 2% to 5% background rate of rare SCN5A nonsynonymous single nucleotide variants (nsSNVs) among healthy individuals confounds clinical genetic testing. Therefore, the purpose of this study was to enhance interpretation of SCN5A nsSNVs for clinical genetic testing using estimated predictive values derived from protein-topology and 7 in silico tools.

Methods and results

Seven in silico tools were used to assign pathogenic/benign status to nsSNVs from 2888 long-QT syndrome cases, 2111 Brugada syndrome cases, and 8975 controls. Estimated predictive values were determined for each tool across the entire SCN5A-encoded Na(v)1.5 channel as well as for specific topographical regions. In addition, the in silico tools were assessed for their ability to correlate with cellul

SUBMITTER: Kapplinger JD 

PROVIDER: S-EPMC4878676 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature