Fig. 2

a) Structure of ADPRHL2 gene (cDNA GenBank: NM_017825.2) with identified variants in exonic regions. The novel identified variant as the uncertain significance (VUS) (c.636_639del) in the ADPRHL2 gene is illustrated in exon 4. The encoded protein involves 363 amino acids in two distinct domains: mitochondrial targeting sequence (MTS) and ADP ribosyl GH. The red section shows the location of the variant in the protein level. This variant causes loss of AA from the red section to the end of the C-terminal region. Other important identified variants are depicted in this figure. b) Nucleotide alignment shows high conservation of the codon residue in vertebrates which encodes protein AA resided after Leucine 212. The Yellow highlighted region indicates the deleted nucleotides. The ConSurf server was used to calculate conservation scores for the amino acid residues affected by the deletion. Scores ranged from 1 to 9, where an average score of 9 represents a highly conserved residue. ConSurf demonstrates evolutionary conservation profiles according to the phylogenetic relations between homologous sequences as well as amino acid’s structural and functional importance. c) Overview of variant filtering of whole-exome sequencing adapted to narrow down to most promising causative variants in the family. To show this that the possible variant might be inherited as dominant, the homozygote variants were filtered against but it did not result in any relevant variant which can justify the brain abnormality