Characterization of lung cancer associated mt-tRNA mutations_
| tRNA Species | Sequence Alteration | Location | Conservation Index (%) | Frequency (%) |
|---|---|---|---|---|
| tRNAAla | T5655C | Acceptor arm | 100.0 | 0.5 |
| tRNAArg | T10454C | T loop | 100.0 | 1.0 |
| tRNALeu(CUN) | A12330G | Acceptor arm | 100.0 | 1.5 |
| tRNASer(UCN) | T7505C | DHU stem | 100.0 | 0.5 |
| tRNAThr | G15927A | Anticodon stem | 100.0 | 2.0 |
The pathogenicity scoring system for the mt-tRNA mutations for lung cancer_
| Scoring Criteria | T5655C | Score Score out of 20. | T10454C | Score Score out of 20. | A12330G | Score Score out of 20. | T7505C | Score Score out of 20. | G15927A | Score Score out of 20. | Classification |
|---|---|---|---|---|---|---|---|---|---|---|---|
| More than one independent report | yes | 2 | yes | 2 | yes | 2 | yes | 2 | yes | 2 | - |
| Evolutionary conservation of the bp | no changes | 2 | no changes | 2 | no changes | 2 | no changes | 2 | no changes | 2 | – |
| Variant heteroplasmy | no | 0 | no | 0 | no | 0 | no | 2 | no | 2 | ≤6 points: neutral polymorphisms |
| Segregation of the mutation with disease | yes | 2 | yes | 2 | yes | 2 | yes | 2 | yes | 2 | 7-10 points: possibly pathogenic |
| Histochemical evidence of mt disease | no evidence | 0 | no | 0 | yes | 2 | no | 0 | no evidence | 0 | ≥ 11 points: definitely pathogenic |
| Biochemical defect in complexes I, III or IV | no | 0 | no | 0 | yes | 2 | no | 0 | yes | 2 | – |
| Evidence of mutation segregation with biochemical defect from single-fiber studies | no | 0 | no | 0 | yes | 2 | no | 0 | yes | 2 | – |
| Mutant tRNA steady-state level of evidence of pathogenicity in transmt cybrid studies | strong evidence | 5 | no | 0 | no | 0 | strong evidence | 5 | strong evidence | 5 | – |
| Maximum score | definitely pathogenic | Ρ | neutral polymorphism | 6 | definitely pathogenic | 14 | definitely pathogenic | 11 | definitely pathogenic | 15 |