Fig. 3

Mutations reported for human HMGCL. ^a: c.27del has been demonstrated by Pospísilová et al. 2003 to lead to a frame shift [39]. This mutation leads to a frameshift and premature stop codon after 32 amino acids without degradation of the DNA, while p.(Arg10Glyfs*24) would be predicted. ^b: associated with skipping of exon 2 [15]. ^c: Likely to affect splicing, although not proven [40]. ^d: Has been named p.Val168Valfs8 by Puisac et al. 2013; may also cause skipping of exon 5 or of exons 5 and 6 (the latter resulting in a physiological mRNA transcript according to [41]. ^e: According to Buesa et al. 1996 aberrant splicing, which mostly results in skipping of exon 9, p.(Met251_Thr292del,), but to a small extent in insertion of 17 amino acids, which precede a stop codon: p.(fs*18) [42]. Not displayed: -Pie et al. (1997) reported a 84 bp in-frame deletion on the mRNA level leads to the loss of 28 amino acids (Val-21 to Lys-48) in the mature protein [43]. This deleted region includes the last of the leader peptide of the precursor HL protein and 21 amino acids of the N-terminus of the mature protein. -Deletion (between intron 1 and intron 4) NG_013061: g.9326_13806del reported by Aoyama et al. 2015 [44]. - Mutation r.61-144del identified on the RNA level only [2]. - As the skipping of exons 5-6b skipping of exons 5–7 has been reported for a physiological alternative transcript [41]. Note: Zaferiou et al. 2007 referred to a ‘C-to-T transition’ which actually should be c.796C > T and is indicated as such in this figure [45]. Roland et al. 2017: c.438 T > G, p.(Ser46Arg) was corrected to p.(Ser146Arg) [37]