Novel variants in tRNA genes and tentative prediction of impact according to the level of nucleotide conservation of the affected position
| Gene | Sequence variation | Gene reading | Structural domains in tRNA | Position in tRNA | Change in tRNA | Nucleotide conservation | Tentative prediction |
|---|---|---|---|---|---|---|---|
| MTTF | m.579T>C | Direct | Acc stem | 3 | T>C | 90%<x<100%, Y or R | Possibly pathological |
| m.592C>T | Direct | D loop | 16 | C>T | <50% | Polymorphism | |
| m.593T>C | Direct | D loop | 17 | T>C | <50% | Polymorphism | |
| m.645A>G | Direct | Acc stem | 71 | A>G | 90%<x<100%, all R | Possibly pathological | |
| MTTV | m.1628C>T | Direct | Anticd stem | 29 | C>T | <50% | Polymorphism |
| m.1645A>G | Direct | Variable region | 46 | A>G | 100%A | Possibly pathological | |
| MTTL1 | m.3258T>C | Direct | Anticd stem | 27 | T>C | 90%<x<100%, all R | Possibly pathological |
| MTTQ | m.4354C>T | Inverse | Variable region | 48 | G>A | <50% | Polymorphism |
| m.4394C>A | Inverse | Acc stem | 7 | G>T | <50% | Polymorphism | |
| MTTM | m.4449G>A | Direct | T stem | 52 | G>A | 100%G | Possibly pathological |
| MTTW | m.5527A>G | Direct | D loop | 16 | A>G | 50%<x<90%, Y or R | Probable polymorphism |
| m.5542C>T | Direct | Anticd loop | 32 | C>T | 100%C | Possibly pathological | |
| m.5560G>A | Direct | T stem | 51 | G>A | 50%<x<90%, all R | Probable polymorphism | |
| m.5574T>C | Direct | Acc stem | 68 | T>C | 50%<x<90%, all Y | Probable polymorphism | |
| MTTA | m.5605A>G | Inverse | T loop | 55 | T>C | 90%<x<100%, Y or R | Possibly pathological |
| m.5608C>T | Inverse | T stem | 52 | G>A | 50%<x<90%, all R | Probable polymorphism | |
| MTTN | m.5663C>T | Inverse | Acc stem | 67 | G>A | 50%<x<90%, all R | Probable polymorphism |
| m.5690A>G | Inverse | Anticd stem | 40 | T>C | 100%T | Possibly pathological | |
| MTTC | m.5793A>G | Inverse | T loop | 60 | T>C | <50% | Polymorphism |
| m.5800A>G | Inverse | Anticd loop | 32 | T>C | 90%<x<100%, all Y | Possibly pathological | |
| MTTY | m.5865T>C | Inverse | Anticd stem | 31 | A>G | 90%<x<100%, all R | Possibly pathological |
| MTTS1 | m.7455A>G | Inverse | T stem | 64 | T>C | 90%<x<100%, all Y | Possibly pathological |
| MTTD | m.7567C>T | Direct | T loop | 54 | C>T | 50%<x<90%, Y or R | Probable polymorphism |
| MTTK | m.8306T>C | Direct | D-stem | 12 | T>C | 100%T | Possibly pathological |
| MTTH | m.12168G>A | Direct | Anticd loop | 34 | G>A | 100%G | Possibly pathological* |
| m.12173T>C | Direct | Anticd stem | 39 | T>C | 50%<x<90%, Y or R | Probable polymorphism | |
| m.12174C>T | Direct | Anticd stem | 40 | C>T | 90%<x<100%, all Y | Possibly pathological | |
| m.12197_12198InsC | Direct | T stem | 64–65 | Ins C | / | Probable polymorphism | |
| MTTL2 | m.12324C>T | Direct | T stem | 61 | C>T | 100%C | Possibly pathological |
| MTTE | m.14697C>T | Inverse | T stem | 50 | G>A | 50%<x<90%, Y or R | Probable polymorphism |
| MTTT | m.15916T>C | Direct | Anticd stem | 31 | T>C | 50%<x<90%, all Y | Probable polymorphism |
| m.15926C>T | Direct | Anticd stem | 41 | T>C | 90%<x<100%, all Y | Possibly pathological | |
| m.15936A>T | Direct | T stem | 52 | A>T | 50%<x<90%, Y or R | Probable polymorphism | |
| m.15947A>G | Direct | Acc stem | 67 | A>G | 50%<x<90%, Y or R | Probable polymorphism | |
| MTTP | m.15977C>T | Inverse | T stem | 50 | G>A | 50%<x<90%, all R | Probable polymorphism |
| m.15992A>T | Inverse | Anticd loop | 34 | T>A | 100%T | Possibly pathological* |
Nucleotide conservations are retrieved from the compilation of tRNA genes of each specificity taking into account 150 mammalian mitochondrial genomes (http://mamit-trna.u-strasbg.fr/).26 ,27 Four levels of conservation are considered. Whenever a nucleotide is conserved in more than 90% of the sequences, the tentative prediction is that the probability of having a structural or functional role is high. Its mutation may thus possibly have pathological consequences. Possible pathological variants are shown in italic.
*Position 34 corresponds to the first nucleotide of the tRNA anticodon triplet. The mutations concerning both MTTH and MTTP do not affect the codon reading. However, they may affect the efficiency of aminoacylation or of post-transcriptional modification, leading to less efficient translation.
Acc stem, acceptor stem; Anticd loop, anticodon loop; Anticd stem, anticodon stem; R, purine base; Y, pyrimidic base.