Single-nucleotide polymorphisms (SNPs) play a major role in the understanding of the genetic basis of many complex human diseases. It is still a major challenge to identify the functional SNPs in disease-related genes. In this review, the genetic variation that can alter the expression and the function of the genes, namely KCNQ1, KCNH2, SCN5A, KCNE1 and KCNE2, with the potential role for the development of congenital long QT syndrome (LQTS) was analyzed. Of the total of 3,309 SNPs in all five genes, 27 non-synonymous SNPs (nsSNPs) in the coding region and 44 SNPs in the 5' and 3' un-translated regions (UTR) were identified as functionally significant. SIFT and PolyPhen programs were used to analyze the nsSNPs and FastSNP; UTR scan programs were used to compute SNPs in the 5' and 3' untranslated regions. Of the five selected genes, KCNQ1 has the highest number of 26 haplotype blocks and 6 tag SNPs with a complete linkage disequilibrium value. The gene SCN5A has ten haplotype blocks and four tag SNPs. Both KCNE1 and KCNE2 genes have only one haplotype block and four tag SNPs. Four haplotype blocks and two tag SNPs were obtained for KCNH2 gene. Also, this review reports the copy number variations (CNVs), expressed sequence tags (ESTs) and genome survey sequences (GSS) of the selected genes. These computational methods are in good agreement with experimental works reported earlier concerning LQTS. © 2009 Springer Science+Business Media B.V.