Bayesian models for syndrome- and gene-specific probabilities of novel variant pathogenicity

Table 1 Estimated burden of rare variants in cases and controls, for the calculation of prior odds of pathogenicity

The estimated burden of rare variants in genes for LQTS, HCM and BrS in cases and ESP controls, where rare corresponds to an allele frequency <0.0005. Burdens are given as proportions (range 0-1). Values are presented for radical (truncating) variants and for inframe indels and missense substitutions combined (non-radical variants). For all genes, an estimate of the burden in cases is derived from the literature. For five LQTS genes, the burden in cases is estimated both from literature reports and from a prospective case series; the latter are used in our model where available. Otherwise half the literature-based estimate is used for LQTS genes (see text for discussion). Zero values of control frequencies are replaced by 0.0002 to compute ratios. For HCM and BrS the burden in cases is taken from the literature, and the burden in controls is fixed at 0.01.

ISSN: 1756-994X