**2.5. Data analysis**

The University of California, Santa Cruz (UCSC), genome browser (http://genome.ucsc.edu) was used for variant analysis and variants were cross-checked against databases including the NHLBI-Extended Sequencing Project (ESP), 1000 Genomes Project Database [31] and the Database of Single-Nucleotide Polymorphisms (dbSNP, http://www.ncbi.nlm.nih.gov/SNP/). Bioinformatic tools, Sorting Intolerant From Tolerant (SIFT, http://sift.jcvi.org/) [32], Polymor‐ phism Phenotyping-2 (PolyPhen-2, http://genetics.bwh.harvard.edu/pph2/) [33] and Mutation taster (http://www.mutationtaster.org/) [34] were used to predict variant effects on protein structure and function in the cases of variants lacking published literature.
