PMC6889285_01
The updated SCN1A annotation identified 10 exons and five shifted splice junctions, increasing the genomic footprint of SCN1A transcription by ~3 kb. All features are described with respect to existing Ensembl model ENST00000303395 and numbered according to the scheme used in Table 1. For clarity, the features are shown as truncated models containing only the exons of specific interest (and certain features are present on multiple transcript models in the complete gene annotation). UTR sequences are shown in grey, coding or NMD regions in black. Features [1] and [2] represent previously unreported 5' UTR sequences that have conservation and equivalent expression in mouse and chicken. Features [7] and [14] are cassette exons predicted to invoke NMD and contain the de novo variants identified in the study within patients one and two respectively. Feature 9 is a cassette exon that is an ancient duplication of coding exon five, to which it is transcribed in a mutually exclusive manner; the clinical significance of this exon has been previously demonstrated by Tate et al. Feature 12 is a cassette exon predicted to invoke NMD. Intron and exon sizes are to approximate scale. Additional transcript models have been omitted for clarity.
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PMC6889285_02_41525_2019_106_Fig3_HTML.jpg
Fig3
Table 1, Figs. 3 and 4). The variant was validated with
Variants in coding regions are associated with DS. a Pedigrees and Sanger sequencing traces of the two families with a de novo SCN1A variant in the identified poison exons. b The two transcripts containing the variants, relative to the full-length transcript. Red exons are coding, white exons are non-coding. c Variants are predicted to disrupt a hnRNP A1 recognition site.
41525_2019_106_Fig4_HTML.jpg
PMC6889285_02_41525_2019_106_Fig4_HTML.jpg
Fig4
Table 1, Figs. 3 and 4). The variant was validated with
PMC6889285_02
The updated SCN1A annotation identified 10 exons and five shifted splice junctions, increasing the genomic footprint of SCN1A transcription by ~3 kb. All features are described with respect to existing Ensembl model ENST00000303395 and numbered according to the scheme used in Table 1. For clarity, the features are shown as truncated models containing only the exons of specific interest (and certain features are present on multiple transcript models in the complete gene annotation). UTR sequences are shown in grey, coding or NMD regions in black. Features [1] and [2] represent previously unreported 5' UTR sequences that have conservation and equivalent expression in mouse and chicken. Features [7] and [14] are cassette exons predicted to invoke NMD and contain the de novo variants identified in the study within patients one and two respectively. Feature 9 is a cassette exon that is an ancient duplication of coding exon five, to which it is transcribed in a mutually exclusive manner; the clinical significance of this exon has been previously demonstrated by Tate et al. Feature 12 is a cassette exon predicted to invoke NMD. Intron and exon sizes are to approximate scale. Additional transcript models have been omitted for clarity.
41525_2019_106_Fig3_HTML.jpg
PMC6889285_02_41525_2019_106_Fig3_HTML.jpg
Fig3
Table 1, Figs. 3 and 4). The variant was validated with
Variants in coding regions are associated with DS. a Pedigrees and Sanger sequencing traces of the two families with a de novo SCN1A variant in the identified poison exons. b The two transcripts containing the variants, relative to the full-length transcript. Red exons are coding, white exons are non-coding. c Variants are predicted to disrupt a hnRNP A1 recognition site.
41525_2019_106_Fig4_HTML.jpg
PMC6889285_02_41525_2019_106_Fig4_HTML.jpg
Fig4
Table 1, Figs. 3 and 4). The variant was validated with