Table 3.
Enzyme activities, in silico prediction of the effect on protein structure, and final prediction of the phenotype for the novel mutations and for the common mutations used as a reference (in bold).
| Mutation (cDNA) | Protein change | Location in the protein | In silico prediction | Enzyme activity | Phenotype prediction (hemizygous/homozygous state) | |
|---|---|---|---|---|---|---|
| 17OHP | Prog | |||||
| c.43G>A | p.Ala15Thr | First hydrophobic domain | ND | 100 (0) | 96 (6) | Normal variant (NV) |
| c.34C>A | p.Leu12Met | First hydrophobic domain | ND | 99 (1) | 100 (1) | NV |
| c.800C>T | p.Pro267Leu | Loop between α-helix H and α-helix I | No effect | 97 (1) | 87 (7) | NV/very mild NC |
| c.46C>T | p.Arg16Cys | First hydrophobic domain | ND | 95 (3) | 81 (3) | NV/very mild NC |
| c.301_302TC>AA | p.Ser101Asn | Loop between α-helix B′ and α-helix C | Minor effect | 94 (3) | 74 (2) | NV/very mild NC |
| c.1444C>T | p.Pro482Ser | β-sheet β9 | ND | 91 (6) | 61 (6) | Very mild NC |
| c.604A>G | p.Ser202Gly | Loop between α-helix F and α-helix F′ | Minor effect | 85 (2) | 81 (3) | Very mild NC |
| c.1349C>T | p.Thr450Met | β-sheet β8 | Minor effect | 78 (6) | 43 (5) | Mild NC |
| c.1357C>T | p.Pro453Ser | β-sheet β8 | ND | 73 (8) | 34 (10) | NC |
| c.841G>T | p.Val281Leu | α-helix I | ND | 57 (8) | 29 (5) | NC |
| c.338C>T | p.Ser113Phe | Loop between α-helix B′ and α-helix C | Severe effect; interferes with active site helices | 4 (1) | 4 (2) | CL |
| c.1348A>C | p.Thr450Pro | β-sheet β8 | Very severe effect | <1 | <1 | CL |
| c.515T>A | p.Ile172Asn | α-helix E | ND | <1 | <1 | CL |
| c.1165_1173delCAAGGCGCC | p.Gln389_Ala391del | α-helix L | Deleterious | 0 | <1 | CL |
Enzyme activity is expressed in % of wild-type activity, with values presented as mean (1SD) of at least four independent experiments. ND: not determined. Mutations are ordered according to the residual enzyme activity with the reference mutations in bold.