Table 5 Criteria for the confirmation of CMMRD.
Genotype | MMR gene genetic testing reason | |||||
|---|---|---|---|---|---|---|
Germline MMR gene variants identified (if two variants are identified, they must be confirmed to be in trans) | C4CMMRD criteria for cancer patient fulfilled (Rec. 1) | Cancer < 18 years with paediatric high TMB (Rec. 2) | Cancer with MMR protein expression loss in neoplastic and non-neoplastic cells including tumour infiltrating lymphocytes and/or endothelial cells (Rec. 3) | Cancer < 18 years with heterozygous germline MMR gene (L)PV (Rec. 4) | C4CMMRD criteria for children without cancer suspected to have NF1/Legius syndrome and a negative NF1/SPRED1 mutation analysis (Rec. 6) | Incidental finding in WES or WGS performed for other reasons in a patient without cancer |
PV/PV | √ | √ | √ | √ | √ | √ |
PV/LPV | √ | √(PPAP-) | √ | √ | √ | √(AT + ) |
LPV/LPV | √ | √(PPAP-) | √(AT + ) | √(AT + ) | √(AT + ) | √(AT + ) |
(L)PV/VUS | √(AT + ) | √(AT + ) | √(AT + ) | √(AT + ) | √(AT + ) | √(AT + ) |
VUS/VUS | √(AT + ) | √(AT + ) | √(AT + ) | NA | √(AT + ) | NA |
(L)PV/X | √(AT + ; mRNA + ) | √(AT + ; mRNA + ) | √(AT + ; mRNA + ) | √(AT + ; mRNA + ) | √(AT + ; mRNA + ) | NA |
VUS/X | √(AT + ; mRNA + ) | √(AT + ; mRNA + ) | √(AT + ; mRNA + ) | NA | √(AT + ; mRNA + ) | NA |
X/X | √(AT + ; mRNA + ) | √(AT + ; mRNA + ) | √(AT + ; mRNA + ) | NA | √(AT + ; mRNA + ) | NA |
