Supplementary Figure 2: Effects of start-proximal PTCs on NMD efficiency.

(a) In genes with 3′ UTR introns, the penultimate EJC becomes the NMD-inducing EJC, as observed in Geuvadis germline variants. (b–e) The start-proximal effect on NMD evasion is evident in additional data sets and is associated with downstream in-frame stop codons, demonstrated for somatic frameshifts (b,d) and for germline variants (c,e). (f,g) There is no clear effect of distance to the downstream in-frame start codon (f) or the Kozak sequence (g). (h–k) There is no decrease in NMD efficiency for shorter distances between the PTC (h) and putative PABPC1-binding motifs (i–k) in a hypothetical looped mRNA conformation. In all panels, the blue line is a fit using loess or generalized additive models (Online Methods) and the shaded area is its 95% confidence interval.