Specifically, after informed consent was obtained, blood samples from patients were sent for detailed mutational analysis involving either 12 LQTS genes (KCNQ1, KCNH2, SCN5A, ANK2, KCNE1, KCNE2, CACNA1C, KCNJ2, CAV3, SCN4B, AKAP9, and SNTA1) or 5 LQTS genes (KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2) and were screened for multiple LQTS mutations/polymorphisms. Genetic tests included next-generation DNA sequencing of all of the coding exons. For that, exons and adjacent splice sites of each of the genes were sequenced using a solid-state sequencing-by-synthesis process (Illumina, Inc., San Diego, California). There are over 230 exons to be sequenced in LQTS; 12 gene panels and both alleles of each exon (maternal and paternal) were sequenced simultaneously. Polymerase chain reaction primers flanking each exon of the regions of interest were designed to generate amplicons ranging in size from ∼200 to 600 bp, avoiding any nonunique sequences, as well as positions of known polymorphisms and mutations. The products of all multiplex reactions for a specific patient were pooled. Sequencing itself first required cluster generation, which is the process of attaching individual fragments from a patient's library to a chambered glass slide and replicating them in situ to produce distinct islands of homogeneous fragments. Using the Genome Analyzer II (Illumina, Inc.), sequencing-by-synthesis chemistry was performed in the slide chambers to which the clusters were attached. Each base (A, C, G, or T) added to a growing DNA strand liberates 1 of 4 associated fluorochromes in a local reaction that was captured by photoimaging cycle for each cluster. Photoimaged data from each cluster of molecules were converted to base calls and aligned to a reference sequence for each gene of interest using Illumina-provided software. Various annotation databases (e.g., dbSNP, HGMD, and the rapidly growing local compilations) were used, when possible, to classify nucleotide differences into various categories, ranging from polymorphisms to pathogenic mutations.