Fig. 4

Examples of SNVs and SVs characterized by LRS that were difficult to fully resolve using SRS. a De novo insertion containing an additional copy of CDKL5 exon 3 identified by Hiatt et al. in an individual with intellectual disability [14]. b Complex chromosomal rearrangement including a 126-Mbp pericentric chromosome 6 inversion that contained a 9.3-Mbp region composed of eight segments rearranged in position and orientation identified by Hiatt et al. in an individual with intellectual disability [14]. The same individual also carried two insertional translocations between chromosomes 7 and 9. c De novo inversion predicted to disrupt both CPNE9 and BRPF1 identified by Mizuguchi et al. in two monozygotic twins with Dravet syndrome [16]. d A gene conversion identified by Watson et al. in a fetus with Meckel-Gruber syndrome that did not map well by SRS [12]. LRS identified a likely pathogenic SNV in the intron 5 splice donor site (G, red; haplotype 2) of TMEM231 in trans with a cluster of four missense SNVs (G, red; A, green; C, blue; and T, yellow; haplotype 1)