Supplementary Table 1: Summary of missense variants in participants

Mutation / Protein Change / Gene / Exon / Number of Heterozygotes / Number of Homozygotes / Reported in colon cancer gene variant database / Dysfunctional Effect / Align GVGD Prediction / PolyPhen Prediction / SIFT Prediction / ESP6500 Carrier Frequency
c.47T>G / p.Val16Gly / MLH1 / 1 / 1 / 0 / No / Unknown / Class C65 / probably damaging / DAMAGING / 0
c.590A>G / p.Gln197Arg / MLH1 / 8 / 1 / 0 / No / Unknown / Class C35 / possibly damaging / TOLERATED / 0
c.626A>G / p.Asn209Ser / MLH1 / 8 / 1 / 0 / No / Unknown / Class C45 / benign / TOLERATED / 1
c.637G>A / p.Val213lMet / MLH1 / 8 / 4 / 0 / Yes / Unknown / Class C0 / benign / TOLERATED / 107
c.655A>G / p.Ile219Val / MLH1 / 8 / 795 / 133 / Yes / No / NA / benign / TOLERATED / 0
c.977T>C / p.Val326lAla / MLH1 / 11 / 1 / 0 / Yes / Unknown / Class C25 / benign / DAMAGING / 11
c.1013A>G / p.Asn338Ser / MLH1 / 11 / 2 / 0 / Yes / Unknown / Class C0 / benign / DAMAGING / 1
c.1136A>G / p.Tyr379Cys / MLH1 / 12 / 1 / 0 / Yes / Unknown / Class C25 / possibly damaging / DAMAGING / 2
c.1148T>C / p.Met383Thr / MLH1 / 12 / 1 / 0 / No / Unknown / Class C65 / probably damaging / DAMAGING / 2
c.1151T>A / p.Val384Asp / MLH1 / 12 / 3 / 0 / Yes / Unknown / Class C65 / probably damaging / DAMAGING / 1
c.1166G>A / p.Arg389Gln / MLH1 / 12 / 2 / 0 / Yes / Unknown / Class C0 / possibly damaging / TOLERATED / 4
c.1217G>A / p.Ser406Asn / MLH1 / 12 / 2 / 0 / Yes / Unknown / Class C0 / benign / TOLERATED / 18
c.1321G>A / p.Ala441Thr / MLH1 / 12 / 2 / 0 / Yes / Unknown / Class C0 / benign / TOLERATED / 4
c.1359G>C / p.Lys453Asn / MLH1 / 12 / 1 / 0 / No / Unknown / Class C0 / benign / TOLERATED / 2
c.1379A>C / p.Glu460Ala / MLH1 / 12 / 2 / 0 / No / Unknown / Class C0 / benign / TOLERATED / 1
c.1489C>G / p.Arg497Gly / MLH1 / 13 / 1 / 0 / No / Unknown / Class C45 / possibly damaging / TOLERATED / 0
c.1549G>A / p.Gly517Arg / MLH1 / 13 / 1 / 0 / No / Unknown / Class C0 / benign / TOLERATED / 0
c.1572G>T / p.Met524Ile / MLH1 / 14 / 1 / 0 / No / Unknown / Class C0 / benign / TOLERATED / 0
c.1808C>G / p.Pro603Arg / MLH1 / 16 / 1 / 0 / Yes / Unknown / Class C65 / possibly damaging / DAMAGING / 1
c.1852-1853delAAinsGC / p.Lys618Ala / MLH1 / 16 / 24 / 0 / Yes / Unknown / Class C65 / probably damaging / DAMAGING / 0
c.1870G>C / p.Asp624His / MLH1 / 16 / 1 / 0 / No / Unknown / Class C0 / probably damaging / DAMAGING / 0
c.1937A>G / p.Tyr646Cys / MLH1 / 17 / 1 / 0 / Yes / Unknown / Class C65 / probably damaging / DAMAGING / 0
c.1963A>G / p.Ile655Val / MLH1 / 17 / 1 / 0 / Yes / Unknown / Class C0 / benign / TOLERATED / 42
c.2101C>A / p.Gln701Lys / MLH1 / 18 / 1 / 0 / Yes / Unknown / Class C0 / benign / TOLERATED / 0
c.2106T>A / p.Ser702Arg / MLH1 / 19 / 1 / 0 / No / Unknown / Class C0 / benign / TOLERATED / 0
c.2146G>A / p.Val716Met / MLH1 / 19 / 8 / 0 / Yes / Unknown / Class C0 / possibly damaging / TOLERATED / 18
c.2152C>T / p.His718Tyr / MLH1 / 19 / 4 / 0 / Yes / Unknown / Class C65 / probably damaging / DAMAGING / 272
c.2252A>G / p.Lys751Arg / MLH1 / 19 / 0 / 1 / Yes / Unknown / Class C25 / benign / TOLERATED / 2
c.1A>C / p.Met1Leu / MSH2 / 1 / 1 / 0 / No / Unknown / Class C0 / probably damaging / DAMAGING / 0
c.138C>G / p.His46Gln / MSH2 / 1 / 1 / 0 / Yes / Unknown / Class C15 / probably damaging / DAMAGING / 3
c.166G>A / p.Glu56Lys / MSH2 / 1 / 1 / 0 / No / Unknown / Class C55 / probably damaging / TOLERATED / 0
c.380A>G / p.Asn127Ser / MSH2 / 3 / 1 / 0 / Yes / Unknown / Class C45 / possibly damaging / DAMAGING / 309
c.505A>G / p.Ile169Val / MSH2 / 3 / 1 / 0 / Yes / Unknown / Class C0 / benign / TOLERATED / 0
c.766G>A / p.Ala256Thr / MSH2 / 4 / 1 / 0 / No / Unknown / Class C0 / benign / TOLERATED / 1
c.820A>G / p.Ile274Val / MSH2 / 5 / 1 / 0 / No / Unknown / Class C0 / benign / TOLERATED / 3
c.885C>G / p.Asp295Glu / MSH2 / 5 / 1 / 0 / No / Unknown / Class C35 / possibly damaging / TOLERATED / 1
c.965G>A / p.Gly322Asp / MSH2 / 6 / 48 / 3 / Yes / No / NA / benign / DAMAGING / 144
c.1044G>C / p.Gln348His / MSH2 / 6 / 1 / 0 / No / Unknown / Class C15 / probably damaging / DAMAGING / 0
c.1168C>T / p.Leu390Phe / MSH2 / 7 / 2 / 0 / Yes / Unknown / Class C0 / benign / DAMAGING / 1
c.1270C>T / p.His424Tyr / MSH2 / 7 / 1 / 0 / No / Unknown / Class C0 / benign / TOLERATED / 0
c.1321A>C / p.Thr441Pro / MSH2 / 8 / 1 / 0 / Yes / Unknown / Class C0 / benign / DAMAGING / 0
c.1352A>C / p.Gln451Pro / MSH2 / 8 / 1 / 0 / No / Unknown / Class C0 / probably damaging / TOLERATED / 0
c.1432C>T / p.Leu478Phe / MSH2 / 9 / 1 / 0 / No / Unknown / Class C15 / probably damaging / DAMAGING / 0
c.1461C>G / p.Asp487Glu / MSH2 / 9 / 1 / 0 / Yes / Unknown / Class C0 / benign / TOLERATED / 0
c.1725T>G / p.Asp575Glu / MSH2 / 11 / 1 / 0 / No / Unknown / Class C0 / benign / TOLERATED / 0
c.1748A>G / p.Asn583Ser / MSH2 / 11 / 1 / 0 / Yes / Unknown / Class C0 / benign / TOLERATED / 2
c.1787A>G / p.Asn596Ser / MSH2 / 12 / 1 / 0 / Yes / Unknown / Class C0 / benign / TOLERATED / 3
c.1927G>A / p.Glu643Lys / MSH2 / 12 / 1 / 0 / No / Unknown / Class C55 / probably damaging / DAMAGING / 1
c.2203A>G / p.Ile735Val / MSH2 / 13 / 1 / 0 / No / Unknown / Class C25 / possibly damaging / DAMAGING / 3
c.2279T>G / p.Phe760Cys / MSH2 / 14 / 1 / 0 / No / Unknown / Class C65 / benign / TOLERATED / 0
c.2542G>T / p.Ala848Ser / MSH2 / 15 / 1 / 0 / No / Unknown / Class C65 / possibly damaging / DAMAGING / 0
c.2558A>G / p.Glu853Gly / MSH2 / 15 / 1 / 0 / Yes / Unknown / Class C65 / possibly damaging / DAMAGING / 0
c.2615A>G / p.Lys872Arg / MSH2 / 15 / 1 / 0 / No / Unknown / Class C0 / benign / TOLERATED / 0
c.2728C>A / p.Gln910Lys / MSH2 / 16 / 2 / 0 / No / Unknown / Class C0 / benign / TOLERATED / 0
c.2732T>G / p.Leu911Arg / MSH2 / 16 / 1 / 0 / Yes / Unknown / Class C45 / probably damaging / DAMAGING / 0
c.2749G>A / p.Ala917Thr / MSH2 / 16 / 1 / 0 / No / Unknown / Class C0 / benign / TOLERATED / 0
c.2801C>A / p.Thr934Lys / MSH2 / 16 / 1 / 0 / No / Unknown / Class C0 / benign / *DAMAGING / 0
c.113C>T / p.Pro38Leu / MSH6 / 1 / 1 / 0 / No / Unknown / Class C0 / benign / TOLERATED / 0
c.116G>A / p.Gly39Glu / MSH6 / 1 / 501 / 62 / Yes / No / NA / probably damaging / TOLERATED / 0
c.118G>T / p.Ala40Ser / MSH6 / 1 / 1 / 0 / No / Unknown / Class C0 / possibly damaging / TOLERATED / 0
c.161G>C / p.Gly54Ala / MSH6 / 1 / 1 / 0 / Yes / Unknown / Class C0 / benign / TOLERATED / 0
c.242C>T / p.Ala81Val / MSH6 / 1 / 1 / 0 / No / Unknown / Class C0 / benign / TOLERATED / 0
c.431G>T / p.Ser144Ile / MSH6 / 2 / 7 / 0 / Yes / Unknown / Class C25 / probably damaging / TOLERATED / 13
c.437G>C / p.Arg146Thr / MSH6 / 2 / 1 / 0 / No / Unknown / Class C25 / probably damaging / DAMAGING / 0
c.532C>T / p.Arg178Cys / MSH6 / 3 / 1 / 0 / No / Unknown / Class C25 / probably damaging / TOLERATED / 0
c.650A>G / p.Asp217Gly / MSH6 / 4 / 1 / 0 / No / Unknown / Class C0 / benign / TOLERATED / 0
c.663A>C / p.Glu221Asp / MSH6 / 4 / 1 / 0 / Yes / Unknown / Class C0 / benign / TOLERATED / 11
c.802G>C / p.Asp268His / MSH6 / 4 / 1 / 0 / No / Unknown / Class C0 / probably damaging / DAMAGING / 0
c.884A>G / p.Lys295Arg / MSH6 / 4 / 1 / 0 / Yes / Unknown / Class C25 / possibly damaging / TOLERATED / 0
c.968C>G / p.Thr323Ser / MSH6 / 4 / 1 / 0 / No / Unknown / Class C0 / benign / TOLERATED / 0
c.980C>G / p.Thr327Ser / MSH6 / 4 / 2 / 0 / No / Unknown / Class C0 / benign / TOLERATED / 1
c.1070A>C / p.Asp357Ala / MSH6 / 4 / 1 / 0 / No / Unknown / Class C0 / benign / TOLERATED / 0
c.1186C>G / p.Leu396Val / MSH6 / 4 / 18 / 0 / Yes / No / NA / benign / TOLERATED / 60
c.1474A>G / p.Met492Val / MSH6 / 4 / 1 / 0 / Yes / Unknown / Class C15 / benign / DAMAGING / 0
c.1481C>T / p.Ala494Val / MSH6 / 4 / 1 / 0 / No / Unknown / Class C65 / benign / TOLERATED / 0
c.1508C>G / p.Ser503Cys / MSH6 / 4 / 5 / 0 / Yes / Unknown / Class C25 / probably damaging / DAMAGING / 16
c.1526T>C / p.Val509Ala / MSH6 / 4 / 3 / 0 / Yes / Unknown / Class C65 / probably damaging / DAMAGING / 11
c.1786T>A / p.Phe596Ile / MSH6 / 4 / 1 / 0 / No / Unknown / Class C15 / benign / TOLERATED / 0
c.1825C>A / p.Leu609Ile / MSH6 / 4 / 1 / 0 / No / Unknown / Class C0 / benign / TOLERATED / 0
c.1830G>C / p.Lys610Asn / MSH6 / 4 / 1 / 0 / No / Unknown / Class C65 / benign / TOLERATED / 0
c.1844G>C / p.Cys615Ser / MSH6 / 4 / 1 / 0 / No / Unknown / Class C0 / benign / TOLERATED / 0
c.2189A>G / p.Tyr730Cys / MSH6 / 4 / 1 / 0 / No / Unknown / Class C0 / benign / TOLERATED / 0
c.2391C>A / p.Asp797Glu / MSH6 / 4 / 1 / 0 / No / Unknown / Class C35 / benign / TOLERATED / 0
c.2398G>C / p.Val800Leu / MSH6 / 4 / 2 / 0 / Yes / Unknown / Class C0 / benign / TOLERATED / 2
c.2561A>T / p.Lys854Met / MSH6 / 4 / 1 / 0 / Yes / Unknown / Class C65 / probably damaging / DAMAGING / 5
c.2594T>G / p.Phe865Cys / MSH6 / 4 / 1 / 0 / No / Unknown / Class C65 / possibly damaging / TOLERATED / 0
c.2633T>C / p.Val878Ala / MSH6 / 4 / 17 / 0 / Yes / No / NA / benign / TOLERATED / 71
c.2752C>T / p.His918Tyr / MSH6 / 4 / 1 / 0 / No / Unknown / Class C65 / probably damaging / TOLERATED / 0
c.3151G>A / p.Val1051Ile / MSH6 / 4 / 2 / 0 / No / Unknown / Class C25 / benign / TOLERATED / 0
c.3160A>T / p.Ile1054Phe / MSH6 / 4 / 1 / 0 / No / Unknown / Class C0 / benign / TOLERATED / 4
c.3203G>A / p.Arg1068Gln / MSH6 / 5 / 1 / 0 / No / Unknown / Class C0 / benign / TOLERATED / 0
c.3217C>T / p.Pro1073Ser / MSH6 / 5 / 1 / 0 / No / Unknown / Class C65 / benign / TOLERATED / 8
c.3259C>G / p.Pro1087Ala / MSH6 / 5 / 1 / 0 / No / Unknown / Class C25 / probably damaging / TOLERATED / 0
c.3259C>T / p.Pro1087Ser / MSH6 / 5 / 1 / 0 / Yes / Unknown / Class C65 / possibly damaging / TOLERATED / 4
c.3407A>G / p.Asn1136Ser / MSH6 / 5 / 2 / 0 / No / Unknown / Class C45 / probably damaging / DAMAGING / 0
c.3488A>T / p.Glu1163Val / MSH6 / 6 / 1 / 0 / Yes / Unknown / Class C35 / benign / TOLERATED / 0
c.3722G>A / p.Cys1241Tyr / MSH6 / 8 / 1 / 0 / No / Unknown / Class C65 / probably damaging / DAMAGING / 0
c.3727A>T / p.Thr1243Ser / MSH6 / 8 / 1 / 0 / No / Unknown / Class C55 / benign / TOLERATED / 2
c.3911G>A / p.Arg1304Lys / MSH6 / 9 / 1 / 0 / No / Unknown / Class C25 / benign / TOLERATED / 38
c.3938T>C / p.Ile1313Thr / MSH6 / 9 / 2 / 0 / No / Unknown / Class C65 / possibly damaging / TOLERATED / 0
c.3980A>G / p.Asn1327Ser / MSH6 / 9 / 1 / 0 / No / Unknown / Class C0 / benign / TOLERATED / 0

Supplementary Table 2:Summary of silent variants in participants

Mutation / Gene / Exon / Number of heterozygotes / Number of Homozygotes
c.198C>T / MLH1 / 2 / 1 / 0
c.375A>G / MLH1 / 4 / 1 / 0
c.843A>C / MLH1 / 10 / 2 / 0
c.996C>T / MLH1 / 11 / 1 / 0
c.1164C>T / MLH1 / 12 / 1 / 0
c.1191G>A / MLH1 / 12 / 1 / 0
c.1269G>A / MLH1 / 12 / 2 / 0
c.1284T>C / MLH1 / 12 / 1 / 0
c.1596C>G / MLH1 / 14 / 1 / 0
c.1959G>T / MLH1 / 17 / 60 / 0
c.2055C>T / MLH1 / 18 / 1 / 0
c.6G>T / MSH2 / 1 / 1 / 0
c.181C>G / MSH2 / 1 / 1 / 0
c.198C>T / MSH2 / 1 / 1 / 0
c.339G>A / MSH2 / 2 / 12 / 0
c.382C>G / MSH2 / 3 / 1 / 0
c.573C>T / MSH2 / 3 / 4 / 0
c.984C>T / MSH2 / 6 / 8 / 0
c.1014A>C / MSH2 / 6 / 1 / 0
c.1221C>G / MSH2 / 7 / 1 / 0
c.1242A>T / MSH2 / 7 / 1 / 0
c.1488A>G / MSH2 / 9 / 1 / 0
c.1560A>G / MSH2 / 10 / 1 / 0
c.1563T>C / MSH2 / 10 / 1 / 0
c.1666T>C / MSH2 / 11 / 20 / 0
c.1737A>G / MSH2 / 11 / 3 / 0
c.1863A>T / MSH2 / 12 / 1 / 0
c.2766T>C / MSH2 / 16 / 5 / 0
c.186C>A / MSH6 / 1 / 481 / 64
c.255C>A / MSH6 / 1 / 1 / 0
c.276A>G / MSH6 / 2 / 42 / 64
c.540T>C / MSH6 / 3 / 599 / 126
c.642C>T / MSH6 / 4 / 338 / 22
c.1050C>T / MSH6 / 4 / 1 / 0
c.1164C>T / MSH6 / 4 / 3 / 0
c.1209C>G / MSH6 / 4 / 1 / 0
c.1740G>A / MSH6 / 4 / 1 / 0
c.1875C>T / MSH6 / 4 / 1 / 0
c.2161A>C / MSH6 / 4 / 1 / 0
c.2253T>C / MSH6 / 4 / 4 / 1
c.2268A>C / MSH6 / 4 / 1 / 0
c.2272C>T / MSH6 / 4 / 4 / 0
c.2283G>A / MSH6 / 4 / 1 / 0
c.2526T>G / MSH6 / 4 / 1 / 0
c.2754T>C / MSH6 / 4 / 1 / 0
c.2913G>A / MSH6 / 4 / 1 / 0
c.3306T>A / MSH6 / 5 / 1 / 0
c.3579A>G / MSH6 / 7 / 1 / 0
c.3625C>T / MSH6 / 7 / 2 / 0