Table 2.
Variant-Level Orthogonal Validation of Aldy
| Variant | Variant allele count in development cohort (total chromosomes) |
Variant allele count in validation cohort (total chromosomes) |
Analytical parameters assessed in validation cohort |
||||
|---|---|---|---|---|---|---|---|
| Accuracy, % |
Analytical sensitivity, % (95% CI) |
Analytical specificity, % (95% CI) |
Interassay concordance, % |
Intra-assay concordance, % |
|||
| CYP2B6∗6 (c.516G>T) | 48 (178) | 42 (150) | 100 | 100 (92–100) | 100 (97–100) | 100 | 100 |
| CYP2B6∗8 (c.415A>G) | 1 (178) | 1 (150) | 100 | 100 (21–100) | N/A† | 100 | 100 |
| CYP2B6∗18 (c.983T>C) | 1 (178) | 1 (150) | 100 | 100 (21–100) | 100 (97–100) | 100 | 100 |
| CYP2C8∗2 (c.805A>T) | 0 (76) | 0 (40) | 100 | N/A | 100 (91–100) | 100 | 100 |
| CYP2C8∗3 (c.416G>A) | 9 (76) | 3 (40) | 100 | 100 (44–100) | 100 (91–100) | 100 | 100 |
| CYP2C8∗4 (c.792C>G) | 3 (76) | 1 (40) | 100 | 100 (21–100) | 100 (91–100) | 100 | 100 |
| CYP2C9∗2 (c.430C>T) | 30 (178) | 20 (150) | 100 | 100 (84–100) | 100 (97–100) | 100 | 100 |
| CYP2C9∗3 (c.1075A>C) | 10 (178) | 9 (150) | 100 | 100 (70–100) | 100 (97–100) | 100 | 100 |
| CYP2C9∗5 (c.1080C>G) | 1 (178) | 1 (150) | 100 | 100 (21–100) | 100 (97–100) | 100 | 100 |
| CYP2C9∗6 (c.818del) | 0 (178) | 0 (150) | 100 | N/A | 100 (98–100) | 100 | 100 |
| CYP2C9∗8 (c.449G>A) | 2 (178) | 0 (150) | 100 | N/A | 100 (98–100) | 100 | 100 |
| CYP2C9∗11 (c.1003C>T) | 0 (178) | 0 (150) | 100 | N/A | 100 (98–100) | 100 | 100 |
| CYP2C19∗2 (c.681G>A) | 26 (178) | 15 (150) | 100 | 100 (80–100) | 100 (97–100) | 100 | 100 |
| CYP2C19∗3 (c.636G>A) | 0 (178) | 0 (150) | 100 | N/A | 100 (98–100) | 100 | 100 |
| CYP2C19∗4 (c.1A>G) | 0 (178) | 0 (150) | 100 | N/A | 100 (98–100) | 100 | 100 |
| CYP2C19∗6 (c.395G>A) | 0 (178) | 0 (150) | 100 | N/A | 100 (98–100) | 100 | 100 |
| CYP2C19∗8 (c.358T>C) | 2 (178) | 0 (150) | 100 | N/A | 100 (98–100) | 100 | 100 |
| CYP2C19∗10 (c.680C>T) | 0 (178) | 0 (150) | 100 | N/A | 100 (98–100) | 100 | 100 |
| CYP2C19∗17 (c.-806C>T) | 33 (178) | 35 (150) | 100 | 100 (90–100) | 100 (97–100) | 100 | 100 |
| CYP2C19∗24 (c.1004G>A) | 1 (178) | 0 (150) | 100 | N/A | N/A† | 100 | 100 |
| CYP2D6∗2 (c.886C>T) | 61 (144) | 46 (128) | 100 | 100 (92–100) | 100 (96–100) | 100 | 100 |
| CYP2D6∗2 (c.1457G>C) | 86 (144) | 76 (128) | 100 | 100 (95–100) | 100 (93–100) | 100 | 100 |
| CYP2D6∗3 (c.775del) | 2 (144) | 2 (128) | 100 | 100 (34–100) | 100 (97–100) | 100 | 100 |
| CYP2D6∗4 (c.506-1G>A) | 23 (144) | 28 (128) | 100 | 100 (88–100) | 100 (96–100) | 100 | 100 |
| CYP2D6∗6 (c.454del) | 3 (144) | 1 (128) | 100 | 100 (21–100) | 100 (97–100) | 100 | 100 |
| CYP2D6∗7 (c.971A>C) | 1 (144) | 0 (128) | 100 | N/A | 100 (97–100) | 100 | 100 |
| CYP2D6∗8 (c.505G>T) | 0 (144) | 0 (128) | 100 | N/A | 100 (97–100) | 100 | 100 |
| CYP2D6∗9 (c.841_843del) | 4 (144) | 5 (128) | 100 | 100 (57–100) | 100 (97–100) | 100 | 100 |
| CYP2D6∗10 (c.100C>T) | 25 (144) | 30 (128) | 100 | 100 (89–100) | 100 (96–100) | 100 | 100 |
| CYP2D6∗14 (c.505G>A) | 0 (144) | 0 (128) | 100 | N/A | 100 (97–100) | 100 | 100 |
| CYP2D6∗15 (c.137dup) | 1 (144) | 1 (128) | 100 | 100 (21–100) | N/A† | 100 | 100 |
| CYP2D6∗17 (c.320C>T) | 3 (144) | 3 (128) | 100 | 100 (44–100) | 100 (97–100) | 100 | 100 |
| CYP2D6∗29 (c.1012G>A) | 2 (144) | 0 (128) | 100 | N/A | 100 (97–100) | 100 | 100 |
| CYP2D6∗41 (c.985+39G>A) | 18 (144) | 14 (128) | 100 | 100 (78–100) | 100 (97–100) | 100 | 100 |
| CYP2D6∗59 (c.975G>A) | 1 (144) | 2 (128) | 100 | 100 (34–100) | N/A† | 100 | 100 |
| CYP2D6∗62 (c.1321C>T) | 0 (144) | 1 (128) | 100 | 100 (21–100) | N/A† | 100 | 100 |
| CYP3A4∗2 (c.664T>C) | 0 (178) | 0 (150) | 100 | N/A | 100 (98–100) | 100 | 100 |
| CYP3A4∗22 (c.522-191C>T) | 8 (134) | 5 (118) | 100 | 100 (57–100) | 100 (97–100) | 100 | 100 |
| CYP3A5∗3 (c.219-237A>G) | 154 (178) | 129 (150) | 100 | 100 (97–100) | 100 (85–100) | 100 | 100 |
| CYP3A5∗6 (c.624G>A) | 2 (178) | 3 (150) | 100 | 100 (44–100) | 100 (97–100) | 100 | 100 |
| CYP3A5∗7 (c.1035dup) | 1 (178) | 0 (150) | 100 | N/A | 100 (98–100) | 100 | 100 |
| CYP4F2∗3 (c.1297G>A) | 41 (178) | 40 (150) | 100 | 100 (91–100) | 100 (97–100) | 100 | 100 |
| DPYD∗2 (c.1905+1G>A) | 0 (178) | 0 (150) | 100 | N/A | 100 (98–100) | 100 | 100 |
| DPYD∗13 (c.1679T>G) | 0 (90) | 0 (136) | 100 | N/A | 100 (97–100) | 100 | 100 |
| DPYD HapB3 (c.1236G>A) | 2 (90) | 0 (136) | 100 | N/A | N/A† | 100 | 100 |
| DPYD D949V (c.2846A>T) | 3 (90) | 1 (136) | 100 | 100 (21–100) | 100 (97–100) | 100 | 100 |
| G6PD A- (c.202G>A) | 3 (134) | 0 (111) | 100 | N/A | 100 (98–100) | 100 | 100 |
| G6PD A- (c.968T>C) | 1 (134) | 0 (111) | 100 | N/A | N/A† | 100 | 100 |
| G6PD A (c.376A>G) | 8 (134) | 4 (111) | 100 | 100 (51–100) | 100 (97–100) | 100 | 100 |
| NUDT15∗3 (c.415C>T) | 2 (30) | 1 (134) | 100 | 100 (21–100) | 100 (97–100) | 100 | 100 |
| NUDT15∗5 (c.52G>A) | 0 (30) | 0 (134) | 100 | N/A | 100 (97–100) | 100 | 100 |
| NUDT15∗9 (c.38GAGTCG[2]) | 2 (30) | 0 (134) | 100 | N/A | N/A† | 100 | 100 |
| SLCO1B1∗5 (c.521T>C) | 28 (178) | 16 (150) | 100 | 100 (81–100) | 100 (97–100) | 100 | 100 |
| TPMT∗2 (c.238G>C) | 0 (178) | 0 (150) | 100 | N/A | 100 (98–100) | 100 | 100 |
| TPMT∗3A,∗3B (c.460G>A) | 9 (178) | 5 (150) | 100 | 100 (57–100) | 100 (97–100) | 100 | 100 |
| TPMT∗3A,∗3C (c.719A>G) | 9 (178) | 5 (150) | 100 | 100 (57–100) | 100 (97–100) | 100 | 100 |
N/A, not applicable.
†
Analytical specificity was not calculated for these alleles because orthogonal validation was only performed on subjects having the allele based on Aldy results.