Table 2.
Study Participants Exhibiting Missense Variants in Both TFV and FTC Activating Kinases
| Racial and ethnic self-identification | Sex assigned at birth | Drug activated | Kinase | Protein position | Amino acid substitution (ref.>alt.) | SIFT prediction | PolyPhen prediction |
|---|---|---|---|---|---|---|---|
| White | Male | TFV | AK2 | 157 | N > S | Tolerated (0.15) | Benign (0.001) |
| FTC | CMPK1 | 66 | A > S | Deleterious (0) | Possibly_damaging (0.901) | ||
| Black or African | Male | TFV | PKLR | 406 | G > W | Deleterious (0) | Probably_damaging (1) |
| FTC | CMPK1 | 74 | R > S | Deleterious (0.03) | Probably_damaging (0.999) | ||
| FTC | CMPK1 | 66 | A > S | Deleterious (0) | Possibly_damaging (0.901) | ||
| Multiracial | Male | TFV | PKLR | 272 | L > V | Deleterious (0) | Probably_damaging (0.974) |
| FTC | DCK | 24 | I > V | Tolerated (0.65) | Benign (0.002) | ||
| FTC | DCK | 122 | P > S | Tolerated (0.06) | Probably_damaging (1) | ||
| FTC | CMPK1 | 166 | R > S | Deleterious (0) | Probably_damaging (0.999) | ||
| FTC | PGK1 | 61 | M > I | Tolerated (0.1) | Benign (0.062) | ||
| White | Male | TFV | AK2 | 209 | A > T | Tolerated (0.5) | Benign (0.056) |
| TFV | PKM | 36 | T > S | N/A | N/A | ||
| TFV | PKLR | 133 | N > K | Deleterious (0.03) | Probably_damaging (0.999) | ||
| FTC | CMPK1 | 115 | N > S | Tolerated (0.84) | Benign (0.001) |
Four study participants were found to simultaneously carry variants in the kinases that activate TFV and FTC. The functional consequence of resulting amino acid exchanges were predicted using SIFT and PolyPhen in silico tools. A SIFT score <0.05 was suggestive of a damaging amino acid substitution and >0.05 a tolerated substitution. A PolyPhen score >0.908 was suggestive of a probably damaging, 0.447–0.908 a possibly damaging, or <0.447 a benign amino acid substitution.
TFV, tenofovir; FTC, fumarate and emtricitabine.