Table 1.

Germline variants identified in each subgroup of SPS.

Preferential Location of Lesions	Pathogenicity	Number of Patients with PV/LPV or with VUS *	Germline Variants (PV/LPV or VUS *)
SPS-FHP/CRC
Proximal/ whole-colon	PV/LPV	4/25 (16%)	ATM: c.4776 + 2T > C MITF: c.1255G > A p.(Glu419Lys) RAD51C: c.890_899del p.(Leu297HisfsTer2) RNF43: c.887dup p.(Asn297Ter)
	VUS *	11/25 (44%)	BLM: c.43C > T p.(Arg15Cys); c.2561G > A p.(Ser854Asn) BRCA1: c.4084G > A p.(Asp1362Asn FANCA: c.3551G > C p.(Arg1184Pro) FANCD2: c.2273G > C p.(Cys758Ser) MSH2: c.2210 + 5G > C PALB2: c.101G > A p.(Arg34His) PDGFRA: c.2212G > T p.(Asp738Tyr) RAD51D: c.493C > T p.(Arg165Trp); c.793G > A p.(Gly265Arg) RECQL4: c.1649C > T p.(Ala550Val) WRN: c.272G > C p.(Arg91Thr) XRCC5: c.1123G > T p.(Val375Phe); c.1343-6T > G
Distal	VUS *	1/6 (17%)	PMS2: c.1004A > G p.(Asn335Ser)
SPS without/ unknown FHP/CRC
Proximal/ whole-colon	PV/LPV	2/19 (10%)	FANCM: c.2586_2589del p.(Lys863IlefsTer12) RAD50: c.2165dup p.(Glu723GlyfsTer5)
	VUS *	6/19 (32%)	FAN1: c.3027dup p.(Gly1010TrpfsTer3) FANCA: c.1874G > C p.(Cys625Ser) FANCL: c.288G > T p.(Lys96Asn) PALB2: c.100C > T p.(Arg34Cys) PTCH1: c.2176C > T p.(Pro726Ser) RAD51C: c.895C > T p.(Pro299Ser)
Distal	VUS *	5/10 (50%)	ATM: c.2735A > G p.(Gln912Arg) ERCC2: c.1606G > A p.(Val536Met) ERCC3: c.847C > T p.(Arg283Cys) FANCA: c.1038G > C p.(Trp346Cys) MSH6: c.2501G > A p.(Ser834Asn) NTHL1: c.556G > A p.(Ala186Thr) (het) TSC2: c.929A > G p.(Tyr310Cys); c.3971T > C p.(Leu1324Pro)

* VUS with prediction of probable damaging effect.