Table 1.
Functional analysis and classification of 21 TP53 variants found in the human populationa.
| TP53_variant | Functional analysisb | Growth suppression (Kotler et al.) | DNE/LOF (Giacomelli et al.) | LOF (Giacomelli et al.) | Population classification (ACMG) | Population classification (ACMG)c | ClinVar datad |
|---|---|---|---|---|---|---|---|
| c.31G>C_E11Q | Functional | No data | Functional | Functional | BA1 (Japan; Korea); BS1(EAS) | Benign (BA1; BS3; BP4) | LB (2) VUS (4) |
| c.91G>A_V31I | Functional | No data | Functional | Functional | BA1 (China; Japan; Korea; Taiwan; gnomAD_EAS) | Benign (BA1; BS3; BP4) | B (1) LB (4) LP (1) VUS (3) Star (1) |
| c.139C>T_P47S | Functional | No data | Functional | Functional | BA1 (Brazil; Flossies; GnomAD; Kaviar; EVS; gnomAD_AFR) | Benign (BA1; BS3; BP4) | B (10) VUS (1) Star (1) |
| c.145G>C_D49H | Functional | No data | Functional | Functional | BA1 (Japan) | Benign (BA1; BS3; BP4) | VUS |
| c.173C>G_P58R | Functional | No data | Functional | Functional | BS1 (gnomAD_AFR; Flossies; EVS) | Benign (BA1; BS3; BP4) | LB (6) VUS (1) |
| c.215C>G_P72R | Functional | No data | Functional | Functional | BA1 (all datasets) | Benign (BA1; BS3; BP4) | B Star (3) |
| c.319T>C_Y107H | Functional | Functional | Functional | Functional | BA1 (gnomAD_AFR); BS1 (Flossies) | Benign (BA1; BS3; BP4) | LB (3) VUS (4) |
| c.329G>A_R110H | Functional | Functional | Functional | Functional | – | Likely benign (BS3; BP4) | VUS |
| c.466C>T_R156C | Functional | Functional | Functional | Functional | – | Likely benign (BS3; BP4) | VUS |
| c.554G>A_S185N | Functional | Functional | Functional | Functional | – | Likely benign (BS3; BP4) | VUS |
| c.566C>T_A189V | Functional | Functional | Functional | Functional | BA1 (China) | Benign (BA1; BS3; BP4) | VUS |
| c.665C>T_P222L | Functional | Functional | Functional | Functional | – | VUS (BS3) | VUS |
| c.704A>G_N235S | Functional | Functional | Functional | Functional | BA1 (Australia); BS1 (FIN; Finland; NFE) | Benign (BA1;BS1;BP4) | B (1)LB (5) VUS (3) Star (1) |
| c.760A>G_I254V | Functional | Functional | Functional | Functional | – | VUS (PP3; BS3) | VUS |
| c.787A>G_N263D | Functional | Functional | Functional | Functional | SAS | Benign (BS1; BS3) | LB (1) VUS (4) |
| c.847C>T_R283C | Functional | Functional | Functional | Functional | EVS | Benign (BS1; BS3) | LB (1) LP (1) VUS (12) |
| c.869G>A_R290H | Functional | Functional | Functional | Functional | BS1 (Finland; Flossies; FIN) | Benign (BS1; BS3) | B (1) LB (1) VUS (10) Star (1) |
| c.935C>G_T312S | Functional | No data | Functional | Functional | BS1 (gnomAD_AFR) | Benign (BS1; BS3) | B (1)LB (1) VUS (4) Star (1) |
| c.1015G>A_E339K | Functional | No data | Functional | Functional | BS1 (gnomAD_EAS) | Benign (BS1; BS3) | LB (2) VUS (3) |
| c.1073A>T_E358V | Functional | No data | Functional | Functional | BA1 (China) | Benign (BA1; BS3; BP4) | LB (1) VUS (2) Star (2) |
| c.1079G>C_G360A | Functional | No data | Functional | Functional | BS1 (gnomAD_LAT; gnomAD_AFR) | Benign (BS1; BS3) | B LB |
| c.524G>A_R175H | Defective | Defective | Defective | Defective | – | Pathogenic (PS3; PS4; PM1; PP3) | P |
| c.761T>C_I254T | Defective | Defective | Defective | Defective | – | Pathogenic (PS3; PS4; PM1; PP3) | No data |
| c.1025G>C_R342P | Defective | Functional | Functional | Defective | – | Pathogenic (PS3; PS4; PM1; PP3) | LP P |
| c.428T>C_V143A | Defective | Defective | Defective | Defective | – | Pathogenic (PS3; PS4; PM1; PP3) | No data |
DNE dominant negative effect, LOF loss of function.
aA complete version of this table with detailed description of all data is available in Table S5.
bFunctional analysis includes transcriptional activity, apoptosis, and cell proliferation assays performed both in human cells or in yeast in the present study.
cFor each classification, identity of the dataset is indicated in brackets. gnomAD data were split into eight geographical datasets (EAS, AFR, SAS, FIN, LAT, EAS, ASJ, and OTH) leading to a total of 22 datasets.
dAssessed June 2020.