Fig. 3

Alternative splicing and potentially damaging human variants in PRKAA2. a Sequences of splice sites observed in canine RNA-seq data. The canonical GT and AG splice site sequences at the exon-intron junctions are indicated in bold. b Schematic representation of canine PRKAA2 transcripts and boundaries of exons 7 and 8: ENSCAFT00000030121.4, exon 7 deletion (chr5:52,820,560–52,820,856, r.729_1024del) mutant, intron 8 retention (chr5:52,818,766–52,818,853, c.1359-1360ins(?)) mutant, and a predicted transcript with both aberrant splice sites (r.(729_1024del;1359_1360ins(?))). c Alternate exon 7 and 8 splicing in the mRNA-seq reads of one affected Dobermann. The aberrant reads are indicated in black. d Proportional expression of the exon 7 mutant transcript detected with ddPCR in five DCM-affected and four unaffected Dobermanns. e Schematic representation of the canine PRKAA2 protein (ENSCAFP00000027993.4, F1PIW7) and the predicted amino acid sequences of the aberrant transcripts. The r.729_1024del variant is predicted to result in truncation upstream of the UBA-like autoinhibitory domain, and the c.1359-1360ins(?) transcript is predicted to contain a premature stop codon before the C-terminal regulatory domain involved in heterotrimerization. Positions corresponding to potentially damaging variants in human cardiomyopathy patients are indicated with black lines. ENSCAFT00000030121.4 was used as a reference sequence for the mutant transcripts, and domain annotation was obtained from CDD