Table 1. Clinical and genetic information of the investigated Tunisian patients and functional variant evaluation.
| Family | Pat-ient | Sex/Age at diagnosis | Tumor location | Results of immunohisto-chemistry | Alteration1 (SNP ID) | Alteration (protein) | Classifi-cation2/ MAPP PP23 | Functional evaluation (supporting evidence) |
|---|---|---|---|---|---|---|---|---|
| A | PIII.6 | Female/52 | Ascend. colon; Cecum | MSI-H Loss of MLH1 and PMS2 | c.2206G>A | p.(Glu736Lys) | No classification/ 0.01 | Functional (functionally neutral, unconserved) |
| B | PIII.3 | Male/50 | Right colon | - | c.1918C>A (rs63749792) | p.(Pro640Thr) | No classification/ 0.83 | Defective (stability decreased like in pathogenic reference variant, highly conserved residue, consistent with role in structure, the similar substitution P640S is already classified “likely pathogenic” |
| C | PIII.4 | Female/45 | Transver. colon | MSI-H Loss of MLH1 and PMS2 | ||||
| D | PIII.3 | Female/46 | Ascend. Colon | MSI-H Loss of MLH1 and PMS2 | ||||
| E | PIII.11 | Male/29 | Left colon | MSI-H Loss of MLH1 and PMS2 | c.218T>C (rs397514684) | p.(Leu73Pro) | class 3 (uncertain) (InSiGHT)/ 0.958 | Defective (stability decreased like in pathogenic reference variant, no MMR activity, consistent with role in protein structure) |
| PIII.5 | Female/21 | Cecum | - |
1gDNA alterations refer to transcript reference sequence NM_000249.3.
2Information on classifications according to InSiGHT consortium, retrieved in April 2022 from the LOVD database.
3MAPP PP2 prior probabilities of pathogenicity according to Thompson et al. [31].