Table 2.
Genetic Diagnoses in 19 Patients With CYP11A1 Mutations
| Subject No. | Genomic Coordinates and Nucleotide Change (Genome Assembly GRCh37.p13) | cDNA Position and Nucleotide Change (Transcript NM_000781) | Protein (Prediction) | dbSNP/HGMD (if Annotated) | Alleles Present in gnomAD; Number Sequenced in gnomAD; MAF gnomAD | Predicteda and/or Tested Consequence | Segregation | Country | Sequencing Method |
|---|---|---|---|---|---|---|---|---|---|
| All | 74635368C>T | 940G>A | E314K | rs6161 | 710; 277190(4 homozygotes);0.002561 | Missensea/skipping of exon 5 = p.A277Dfs*11 | Yes | Various | Various |
| Variants in trans with rs6161 | |||||||||
| 1 | 74635318C>T | 990G>A | T330 = | NA | Not seen;0 | Silenta/skipping of exon 5 p.A277Dfs*11 and NMD | Yes | United Kingdom | WES |
| 2 | 74635473delT | 835delA | I279Yfs*10 | rs757299093/CD050132 | 7; 277156;4.061e-6 | Early stopa | Yes | United Kingdom | HaloPlex |
| 3 | 74631031G>A | 1315C>T | R439* | rs755975808 | 2; 277174;7.216e-6 | Early stopa | Yes | Spain | HaloPlex |
| 4 | 74631641G>A | 1173C>T (ND) | S391 = | rs751829641 | 6; 277178;2.165e-5 | Silenta/skipping exon 7 = p.L387Hfs*29 | ND | United Kingdom | HaloPlex |
| 5A | 74632081A>G | 1004T>C | L335P | NA | Not seen;0 | Missensea | Yes | France | HaloPlex |
| 5B | 74632081A>G | 1004T>C | L335P | NA | Not seen;0 | Missensea | Yes | France | HaloPlex |
| 6 | 74637586T>C | c.426-2A>G | exon 3 skip | rs754329273 | 2; 245202;8.157e-6 | Skipping of exon 3a, resulting in p.K142Nfs*3 | ND | United Kingdom | HaloPlex |
| 7 | 74631076G>A | 1270C>T | R424* | rs762412759 | 5; 277032;1.805e-5 | Truncation/NMDa | ND | United Kingdom | HaloPlex |
| 8A | 74636157_74636169del | c.790_802del | K264Lfs*5 | NA | Not seen;0 | Early stopa | Yes | United Kingdom | HaloPlex |
| 8B | 74636157_74636169del | c.790_802del | K264Lfs*5 | NA | Not seen;0 | Early stopa | Yes | United Kingdom | HaloPlex |
| 8C | 74636157_74636169del | c.790_802del | K264Lfs*5 | NA | Not seen;0 | Early stopa | Yes | United Kingdom | HaloPlex |
| 9 | 74631658T>C | c.1158-2A>G | exon 7 skip | NA | Not seen;0 | Skipping of exon 7 resulting in p.L387Hfs*29a | ND | Turkey | HaloPlex |
| 10A | 74640308G>A | c.358C>T | R120* | NA | 2; 246224;8.123e-6 | Early stop | ND | United Kingdom | HaloPlex |
| 10B | 74640308G>A | c.358C>T | R120* | NA | 2; 246224;8.123e-6 | Early stop | ND | United Kingdom | HaloPlex |
| 11A | 74635473delT | c.835delA | I279Yfs*10 | rs757299093/CD050132 | 7; 277156;4.061e-6 | Early stopa | Yes | Australia | WES |
| 11B | 74635473delT | c.835delA | I279Yfs*10 | rs757299093/CD050132 | 7; 277156;4.061e-6 | Early stopa | Yes | Australia | WES |
| 11C | 74635473delT | c.835delA | I279Yfs*10 | rs757299093/CD050132 | 7; 277156;4.061e-6 | Early stopa | Yes | Australia | WES |
| 12 | 74637444dupG | c.566dupC | S191Lfs*10 | NA | Not seen;0 | Early stop | ND | Canada | CYP11A1 sequencing |
| 13 | 74630968G>A | c. 1378C>T | R460W | rs535782968 | 2; 246170;8.124e-6 | Missensea | ND | United Kingdom | CYP11A1 sequencing |
Abbreviations: NA, not applicable; ND, not determined, WES, whole exome sequencing.
a
Predicted consequence of variant at protein level.