Figure 3.

Summary of rare single nucleotide variants (SNVs) and small insertions and deletions (indels) identified in the novel pulmonary arterial hypertension (PAH) candidate gene KDR (kinase insert domain receptor). A, Only rare predicted deleterious variants in KDR are shown (minor allele frequency [MAF] <1/10 000 and combined annotation dependent depletion [CADD] ≥10). SNVs and indels are represented by colored lollipops on top of the protein sequence. The domain annotations were retrieved from Uniprot (accession number P35968). Lollipop colors indicate the consequence type, and sizes represent the variant frequency within a cohort. Missense variants that are predicted to be deleterious (Sorting Intolerant From Tolerant prediction score [SIFT]) and damaging (PolyPhen-2) are colored in red, otherwise in yellow (ie, SIFT and PolyPhen-2 disagree). High impact variants are labelled with the respective Human Genome Variation Society notation. The number of variants by predicted consequence type and cohort is provided in the table. B, Familial segregation of KDR nonsense variant c.183G>A (p.Trp61*) with PAH (ie, reduced KCO and late onset) from father (W000229) to daughter (W000229.d). Sanger sequencing results are shown in the chromatograms. NBR indicates NIHR BioResource—Rare Diseases; and USBB, US PAH Biobank.