The association between genetic variants in hMLH1 and hMSH2 and the development of sporadic colorectal cancer in the Danish population

Table 5 In silico functional characterization of the missense variants

Id	Variant	PMUT	SIFT	PolyPhen	Phylogeny	Activity in functional assays	References
	MLH1
24	p.Thr117Met	Neutral	Not tolerated	Possible damaging	Conserved	Aberrant	[11,12]
27	p.Val219Ile	Neutral	Tolerated	Benign	Ile other species	Normal	[11,12]
85	p.Ser406Asn	Neutral	Tolerated	Benign	Non-conserved	Normal	[11]
31	p.Glu460Ala	Pathogen	Tolerated	Benign	Non-conserved	NA	-
101	p.Ile563Met	Neutral	Tolerated	Possible damaging	Non-conserved	NA	-
34	p.Lys618Ala	Pathogen	Not tolerated	Possible damaging	Non-conserved	Normal/aberrant	[9,11,45–47]
100	p.Pro648Ser	Pathogen	Not tolerated	Probably damaging	Conserved	Normal (aberrant protein stability)	[9,67]
36	p.His718Tyr	Neutral	Not tolerated	Probably damaging	Conserved	Normal	[11]
	MSH2
89	p.Thr44Met	Neutral	Not tolerated	Possible damaging	Conserved	NA	-
87	p.Ala45Val	Neutral	Tolerated	Benign	Val other species	NA	-
90	p.Arg96His	Pathogen	Tolerated	Probably damaging	Non-conserved	NA	-
91	p.Lys110Arg	Neutral	Tolerated	Benign	Non-conserved	NA	-
92	p.Asn127Ser	Neutral	Not tolerated	Probably damaging	Conserved	NA	-
93	p.Leu187Arg	Neutral	Not tolerated	Probably damaging	Conserved	NA	-
41	p.Gly322Asp	Neutral	Tolerated	Benign	Conserved	Slightly reduced	[8,44]
96	p.Met688Val	Neutral	Not tolerated	Probably damaging	Conserved	NA	-
50	p.Ala834Thr	Pathogen	Tolerated	Possible damaging	Non-conserved	Normal	[10]
51	p.Ala848Ser	Neutral	Not tolerated	Possible damaging	Conserved	NA	-

ISSN: 1471-2350