Table 5.
Functional data- (likely) deleterious mutations in the TP53 gene
| Genomic position | Protein change | DNA domain | Transcriptional activity in yeast (% of wild-type) | Relative fitness score (RFS)** |
|---|---|---|---|---|
| c.375G > A | p.Thr125Thr | DNA-binding domain | Unknown | RFS ≤ − 1 |
| c.542G > A | Arg181His | DNA-binding domain |
Medium reduction (50.3%) |
RFS ≤ − 1 |
| c.700 T > C | Tyr234His | DNA-binding domain |
Very strong reduction (0.89%) |
RFS > − 1 |
| c.717C > G | Asn239Lys | DNA-binding domain |
Moderate strong reduction (26.4%) |
RFS < −1 |
| c.733G > A | Gly245Ser | DNA-binding domain |
Strong reduction (4.2%) |
RFS > − 1 |
| c.742C > T | Arg248Trp | DNA-binding domain |
Very strong reduction (0.09%) |
RFS > − 1 |
| c.743G > A | p.Arg248Gln | DNA-binding domain |
Very strong reduction (0.21%) |
RFS > − 1 |
|
c.783-2A > G splice acceptor |
p.? | DNA-binding domain | Unknown | Unknown |
| c.800G > C | p.Arg267 Pro | DNA-binding domain |
Very strong reduction (0.46%) |
RFS > − 1 |
| c.817C > T | p.273Arg > Cys | DNA-binding domain |
Very strong reduction (0.76%) |
RFS > − 1 |
| c.818G > A | Arg273His | DNA-binding domain | Strong reduction (2.51%) | RFS > − 1 |
RFS ≤ − 1: retaining wtp53-like anti-proliferative functionality
RFS > − 1: disrupting functionality
Hotspot mutations: R175H, R273H, R248Q, R248W, R273C, R282W
**RTS (relative fitness score)