Figure 6

Magnitude of effect sizes estimated from the full LQTS model. A positive effect size indicates that the evidence supports pathogenicity, whereas a negative effect size indicates evidence against pathogenicity. On the left, the effect size for each gene and domain term is shown, with gene effects corresponding to the logarithm of the prior odds for non-radical variants in Table 1 multiplied by a scale parameter. Domains are ordered sequentially according to genome position. The colour of the bars reflects the number of variants in the LQTS training set for each gene or domain: magenta bars are derived from many training variants (indicating high confidence), and grey bars from few variants. The top right panel shows the effect size for other binary variables, i.e. variant class (inframe/missense), allele frequency and conservation classes. The middle right panel includes gene terms for radical variants, where a gene term corresponds to the logarithm of the prior odds for radical variants in Table 1 multiplied by a scale parameter and added to the effect of variant class (radical). Magenta bars imply many training variants, while grey bars indicate few radical variants and white bars denote genes without any radical variants in the LQTS training data. The bottom right panel shows the effect size for continuous predictors (nsSNP algorithms) as linear or quadratic functions of the predictor value. Interd., Interdomain; IQ, IQ calmodulin binding motif, named after the first two amino acids of the motif, isoleucine (I) and glutamine (Q); L., Linker; LQTS, long QT syndrome; PAS, Per-Arnt-Sim domain, named after homology to the Drosophila period protein (PER), the aryl hydrocarbon receptor nuclear translocator protein (ARNT) and the Drosophila single-minded protein (SIM); PPh2, PolyPhen-2; TM, Transmembrane; Transm., Transmembrane; volt., voltage.