Deleterious mismatch repair (MMR) mutations in the Norwegian population22 31
| Type of mutation/ gene | Mutation | Effect of mutation (verified or predicted) | Family No | No of mut+ | IHC (missing protein) | Inclusion criteria: Amsterd.‡‡ | Inclusion criteria: BII §§ | Ref. |
| Frameshift | ||||||||
| MLH1e1 | c.39_40dupGA | p.Thr14ArgfsX3 | H1855 (D4354) | 6 | MLH1/PMS2 | I & II | 1, 2, 4 & 5 | LOVD |
| T343 | 1 | MLH1/PMS2 | I & II | 1, 2, 4 & 5 | ||||
| D20 | 1 | MLH1/PMS2 | I & II | 1, 2, 4 & 5 | ||||
| MLH1e5 | c.413delC | p.Pro138LeufsX21 | U82517 | 1 | MLH1/PMS2 | I & II | 1, 2, 4 & 5 | ¶¶ |
| MLH1e10 | c.866_867delAC | p.His289ProfsX16 | H836 | 2 | MLH1/PMS2 | I & II | 1, 2, 4 & 5 | LOVD |
| MLH1e13 | c.1411_1414delAAGA | p.Lys471AspfsX19 | H892* | 3 | MLH1/PMS2& MSH2/MSH6 | II | 1& 5 | LOVD |
| MLH1e16 | c.1771dupG | p.Asp591GlyfsX1 | U97760 | 3 | MLH1&PMS2 | I & II | 1, 2, 4 & 5 | ¶¶ |
| MSH2e2 | c.229_230delAG | p.Ser77CysfsX3 | H3323 | 1 | MSH2/MSH6 | 0 | 1 | LOVD |
| MSH2e4 | c.675_678delAGAA | p.Thr225ThrfsX19 | D2679 | 1 | MSH2/MSH6 | II | 1, 4 & 5 | ¶¶ |
| MSH2e6 | c.969_970delTC | p. Gln324ValfsX8 | U85816 | 2 | MSH2/MSH6 | I & II | 1, 2, 4 & 5 | ¶¶ |
| D2033 | 1 | MSH2/MSH6 | I & II | 1, 2, 4 & 5 | ||||
| MSH2e7 | c.1204delC | p.Gln402LysfsX10 | H677 | 1 | MSH2/MSH6 | II | 1, 4 & 5 | LOVD |
| MSH2e10 | c.1594dupG | p.Val532GlyfsX3 | D139 | 5 | MSH2/MSH6 | I & II | 1, 2, 4 & 5 | LOVD |
| MSH2e11 | c.1705_1706delGA | p.Glu569IlefsX1 | D2938 | 4 | MSH2/MSH6 | II | 1, 2, 4 & 5 | LOVD |
| MSH2e13 | c.2120_2122delGCA insCGGGCTAAGAAGTG | p.Cys707SerfsX2 | D1570 | 5 | MSH2/MSH6 | I & II | 1, 2, 4 & 5 | ¶¶ |
| MSH6e4 | c.900dupG | p.Lys301GlufsX11 | U88612 | 2 | MSH2/MSH6 | II | 2, 4 & 5 | ¶¶ |
| MSH6e4 | c.1405delT | p.Tyr469IlefsX11 | S254 | 9 | normal† | II | 5 | ¶¶ |
| MSH6e4 | c.1943delG | p.Ser648MetfsX5 | H2327 | 3 | MSH2/MSH6 | 0 | 1, 2 & 4 | ¶¶ |
| MSH6e4 | c.2604delG | p.Met868IlefsX5 | D1731 | 3 | MSH6 | II | 2 & 5 | ¶¶ |
| MSH6e5 | c.3195_3199delCTATA | p.Asn1065LysfsX4 | D2115 | 5 | MSH6 | II | 1, 4 & 5 | LOVD |
| MSH6e5 | c.3261dupC | p.Phe1088LeufsX5 | H1408 | 1 | MSH6 | I & II | 1, 4 & 5 | LOVD |
| S631 | 7 | MSH6 | 0 | 1 & 2 | ||||
| S1108 | 4 | MSH6 | II | 1, 2 & 4 | ||||
| T02 | 2 | MSH2/MSH6 | I & II | 1, 2, 4 & 5 | ||||
| MSH6e5 | 3261delC | p.Phe1088ProfsX2 | D867 | 8 | MSH6 | 0 | 2 & 5 | LOVD |
| MSH6e6 | c.3514dupA | p.Arg1172LysfsX4 | U94618 | 1 | MSH6 | II | 2 | LOVD |
| MSH6e9 | c.3804dupA | p.Cys1269MetfsX5 | U61010 | 7 | MSH2/MSH6 | 0 | 2 & 5 | LOVD |
| U98731 | 2 | MSH6 | II | 2, 4 & 5 | ||||
| U1000922 | 2 | MSH6 | 0 | 0 | ||||
| U1003522 | 1 | MSH6 | 0 | 1 & 5 | ||||
| D1151 | 4 | MSH6 | 0 | 2 & 5 | ||||
| S889 | 1 | MSH6 | 0 | 2 | ||||
| MSH6e9 | c.3832_3845del14 | p.Pro1278_1282delfsX6 | U1000116 | 1 | MSH6 | II | 4 & 5 | ¶¶ |
| PMS2e7 | c.736_741delCCCCCT insTGTGTGTGAAG | p.Pro246CysfsX2 | U97751 | 1 | PMS2 | 0 | 1 & 5 | LOVD |
| PMS2e14 | c.2382dupT | p.Gly795TrpfsX29 | T92 | 3 | PMS2 | 0 | 2 & 5 | ¶¶ |
| Splice defect | ||||||||
| MLH1int9 | c.790+1G→A | Skipping of exon 9-10 | H285 | 2 | ND | 0 | 1, 4 & 5 | LOVD |
| MLH1int9 | c.791–2A→G | Splice defect | T04 (S639 & H1547)) | 8 | MLH1/PMS2 | I & II | 1, 2, 4 & 5 | LOVD |
| MLH1e10 | c.793C→T | p.Arg265Cys‡ | D490 | 10 | MLH1/PMS2 | I & II | 1, 2, 4 & 5 | LOVD |
| MLH1e15 | c.1731G→C | Skipping of exon 15§ | U1001245 | 3 | MLH1/PMS2 | I | 1, 2, 4 & 5 | LOVD (c.1731G→A) |
| MLH1int15 | c.1731+1G→C | Splice defect | D1532 | 1 | MLH1/PMS2 | II | 1, 2, 4 & 5 | LOVD |
| MSH2e5 | c.815C→T | r.(=)+(=; 793_942del)¶ | S403 | 5 | MSH2/MSH6 | 0 | 2, 4 & 5 | LOVD |
| MSH2int5 | c.942+3A→T | r.(=)+(793_942del)¶ | H07 | 5 | ND | II | 1, 2, 4 & 5 | LOVD |
| H892* | 3 | MSH2/MSH6 | II | 1, 2, 4 & 5 | ||||
| H1503 (S551) | 4 | MSH2/MSH6 | 0 | 1, 2, 4 & 5 | ||||
| H1598 (S583) | 3 | MSH2/MSH6 | II | 1, 2, 4 & 5 | ||||
| H2215 | 4 | MSH2/MSH6 | I & II | 1, 2, 4 & 5 | ||||
| H2280 | 1 | MSH2/MSH6 | 0 | 1, 2, 4 & 5 | ||||
| U101185 | 1 | MSH2/MSH6 | II | 1, 4 & 5 | ||||
| T059 | 3 | MSH2/MSH6 | 0 | 1, 4 & 5 | ||||
| T073 | 9 | MSH2/MSH6 | 0 | 1, 2, 4 & 5 | ||||
| D637 | 3 | MSH2/MSH6 | 0 | 4 & 5 | ||||
| D1211 | 11 | MSH2/MSH6 | I & II | 1, 2, 4 & 5 | ||||
| D4522 | 2 | MSH2/MSH6 | 0 | 1, 2 & 5 | ||||
| MSH2int6 | c.1076+1G→A | Skipping of exon 6 | H1903 | 5 | MSH2/MSH6 | 0 | 1, 4 & 5 | LOVD |
| D1773 | 5 | MSH2/MSH6 | 0 | 2 & 5 | ||||
| MSH2int7 | c.1277–2A→G | r.(=, 1277_1386del)¶ | S577 | 9 | MSH2/MSH6 | I & II | 1, 2 & 4 | LOVD |
| S612 | 4 | MSH2/MSH6 | 0 | 1, 2 & 4 | ||||
| D671 | 2 | MSH2/MSH6 | II | 1, 2, 4 & 5 | ||||
| MSH2int10 | c.1661+1G→A | Splice defect | D470 | 2 | MSH2/MSH6 | II | 1, 2, 4 & 5 | LOVD |
| MSH2e11 | c.1759G→C | r.(=, 1662_1759del)§ ¶ | S959 | 2 | MSH2/MSH6 | 0 | 1, 2 & 4 | LOVD |
| MSH2int11 | c.1759+2T→A | Deletion exon 12, 13 | D971 | 1 | MSH2/MSH6 | I & II | 1, 2, 4 & 5 | LOVD |
| MSH2e12 | c.1979A→G | r.(=, 1979_2005del)¶ | U74987 | 1 | MSH2/MSH6 | 0 | 1, 2, 4 & 5 | 31 |
| MSH2int12 | c.2006–1G→C | splice defect | D2013 | 3 | MSH2/MSH6 | I & II | 1, 2, 4 & 5 | LOVD |
| MSH2int15 | c.2634+1G→T | r.(=, 2459_2634del) | H246/275 | 10 | ND | I & II | 1, 4 & 5 | LOVD |
| MSH6int7 | c.3647–2A→C | r.(=, 3646_3647ins3646 +1_3646+492)¶ | S819 (U100998&U104021) | 10 | MSH6 | II | 1, 2 & 4 | LOVD |
| D686 | 7 | MSH6 | II | 0 | ||||
| PMS2intr5 | c.537+1G→T | Splice defect | H3118 | 2 | PMS2 | 0 | 1 | ¶¶ |
| PMS2int9 | c.989–1G→T | r.(=)+(989_1144del, 989_1015del)¶ | S90 | 4 | normal (MSI)** | 0 | 1, 2 & 4 | 22 |
| S335 | 1 | normal (MSI)** | II | 1, 2 | ||||
| S350 | 4 | PMS2 | I & II | 1 & 4 | ||||
| S1147 | 2 | normal (MSI)** | 0 | 1 | ||||
| D3786 | 5 | PMS2 | I & II | 1, 2, 4 & 5 | ||||
| Stop codon | ||||||||
| MLH1e2 | c.184C→T | p.Gln62X | H321 | 8 | ND | I & II | 1, 4 & 5 | LOVD |
| H480 | 4 | ND | I & II | 1, 2, 4 & 5 | ||||
| H487 | 3 | MLH1/PMS2 | I & II | 1, 2, 4 & 5 | ||||
| D498 | 9 | MLH1/PMS2 | I & II | 1, 2, 4 & 5 | ||||
| D874 | 4 | MLH1/PMS2 | I & II | 1, 2, 4 & 5 | ||||
| D1704 | 5 | MLH1/PMS2 | I & II | 1, 2, 4 & 5 | ||||
| MSH2e1 | c.142G→T | p.Glu48X | U1101385 | 1 | MSH2/MSH6 | 0 | 1 & 5 | LOVD |
| U101386 | 1 | MSH2/MSH6 | II | 1, 4 & 5 | ||||
| MSH2e1 | c.181C→T | p.Gln61X | D3959 | 3 | MSH2/MSH6 | II | 1 & 5 | LOVD |
| MSH2e2 | c.226C→T | p.Gln76X | D271 | 2 | MSH2/MSH6 | 0 | 1, 2, 4 & 5 | LOVD |
| MSH2e12 | c.1857T→G | p.Tyr619X | D3648 | 4 | MSH2/MSH6 | 0 | 1, 2, 4 & 5 | LOVD |
| MSH2e13 | c.2038C→T | p.Arg680X | U59124 | 1 | MSH2/MSH6 | I | 1, 2, 4 & 5 | LOVD |
| D414 | 7 | MSH2/MSH6 | I & II | 1, 2, 4 & 5 | ||||
| MSH2e14 | c.2275G→T | p.Gly759X | D1661 | 4 | MSH2/MSH6 | 0 | 1, 2, 4 & 5 | LOVD |
| MSH6e3 | c.467C→G | p.Ser156X | D1651 | 1 | MSH6 | 0 | 5 | LOVD |
| MSH6e4 | c.718C→T | p.Arg240X | D4216 | 2 | MSH6 | 0 | 1, 2, 4 & 5 | LOVD |
| MSH6e4 | c.1444C→T | p.Arg482X | S407 | 5 | MSH2/MSH6 | I & II | 1, 2 & 4 | LOVD |
| S1003 | 10 | MSH6 | 0 | 5 | ||||
| MSH6e4 | c.1483C→T | p.Arg495X | S363 | 5 | MSH2/MSH6 | II | 2 & 4 | LOVD |
| MSH6e4 | c.2731C→T | p.Arg911X | D1316 | 7 | MSH6 | 0 | 1, 2 & 5 | LOVD |
| MSH6e9 | c.3991C→T | p.Arg1331X | H1522 | 5 | ND | 0 | 1, 2 & 4 | LOVD |
| D1826 | 10 | MSH6 | 0 | 5 | ||||
| Exon deletion | ||||||||
| MLH1 | c.546-?_790+?del | del exon 7–9 | S499 (H1102) | 11 | MLH1/PMS2 | I & II | 1, 2, 4 & 5 | LOVD |
| D2020 | 4 | MLH1/PMS2 | I & II | 1, 2, 4 & 5 | ||||
| MLH1 | c.1732-?_1896+?del | del exon 16 | H2094 | 1 | ND | I | 1, 4 & 5 | LOVD |
| MSH2 | c.1-?_366+?del | del exon 1–2 | S541 | 2 | MSH2/MSH6 | 0 | 1, 2 & 4 | LOVD |
| MSH2 | c.1-?_1076+?del | del exon 1–6 | H592 | 3 | MSH2/MSH6 | 0 | 1, 2, 4 & 5 | LOVD |
| D1718 | 4 | MSH2/MSH6 | 0 | 1, 2, 4 & 5 | ||||
| MSH2 | c.1-?_1276+?del | del exon 1–7 | U81431 | 2 | MSH2/MSH6 | I & II | 1, 2, 4 & 5 | LOVD |
| MSH2 | c.1-?_1661+?del | del exon 1-10 | D3824 | 3 | MSH2/MSH6 | 0 | 1 & 5 | LOVD |
| MSH2 | c.212-?_1276+?del | del exon 2-7 | H346 | 3 | ND | I & II | 1, 2, 4 & 5 | LOVD |
| H496 | 1 | MSH2/MSH6 | II | 1, 4 & 5 | ||||
| H1110 (S604) | 9 | MSH2/MSH6 | II | 1, 2, 4 & 5 | ||||
| S81 | 5 | MSH2/MSH6 | I & II | 1, 4 & 5 | ||||
| S281(U1002732) | 8 | MSH2/MSH6 | I & II | 1, 2, 4 & 5 | ||||
| S649 | 6 | MSH2/MSH6 | II | 1, 2 & 4 | ||||
| D2107 | 7 | MSH2/MSH6 | I & II | 1, 2, 4 & 5 | ||||
| MSH2 | c.367-?_645+?del | del exon 3 | H400 | 4 | MSH2/MSH6 | I & II | 1, 4 & 5 | LOVD |
| In-frame deletion | ||||||||
| MSH2e3 | c.571_573delCTC | p.Leu191del | H1294 | 1 | MSH2/MSH6 | I & II | 1, 2, 4 & 5 | ¶¶ |
| H2544 | 1 | MSH2/MSH6 | 0 | 1 & 5 | ||||
| H3517 | 1 | ND | 0 | 4 | ||||
| U90087 | 1 | MSH2/MSH6 | II | 1, 2, 4 & 5 | ||||
| U1000173 | 2 | MSH2/MSH6 | II | 1, 4 & 5 | ||||
| T382 | 3 | MSH2/MSH6 | 0 | 1, 4 & 5 | ||||
| MSH2e12 | c.1786_1788delAAT | p.Asn596del | D554 | 19 | MSH2/MSH6 | I & II | 1, 2, 4 & 5 | LOVD |
| D853 | 5 | MSH2/MSH6 | I & II | 1, 2, 4 & 5 | ||||
| D3618 | 5 | MSH2/MSH6 | I & II | 1, 2, 4 & 5 | ||||
| D3667 | 3 | MSH2/MSH6 | I & II | 1, 2, 4 & 5 | ||||
| D3707 | 7 | MSH2/MSH6 | I & II | 1, 2, 4 & 5 | ||||
| D4202 | 2 | MSH2/MSH6 | II | 1, 2, 4 & 5 | ||||
| MSH6e4 | c.2302_2304delCCT | p.Pro768del | H801 | 2 | MSH2/MSH6 | 0 | 1, 2, 4 & 5 | LOVD |
| 4/14 | H2160 | 5 | ND | 0 | 2, 4 & 5 | |||
| S149 | 5 | MSH2/MSH6 | 0 | 1 & 5 | ||||
| S647 | 3 | MSH2/MSH6 | II | 2 | ||||
| Missense | ||||||||
| MLH1e3 | c.245C→T | p.Thr82Ile | S420†† | 6 | normal (MSI)** | II | 1, 4 & 5 | LOVD |
| MLH1e16 | c.1823C→A | p.Ala608Asp | S581†† | 2 | MLH1/PMS2 | II | 1, 2 & 4 | LOVD |
| MSH6e4 | c.2906A→G | p.Tyr969Cys | D2955†† | 6 | MSH6 | I & II | 1, 2, 4 & 5 | LOVD |
↵* Two pathogenic mutations in two branches in the same family.
↵† No indications from IHC or microsatellite instability.
↵‡ Reported to affect splicing and stability.
↵§ Last nucleotide in exon; reported to cause skipping of exon.
↵¶ Shown in present study to give aberrant splicing.
↵** Normal protein expression, but microsatellite instability.
↵†† Cosegregation with disease.
↵‡‡ Amsterdam I and/or Amsterdam II.
↵§§ Bethesda II (revised), see text for details.
↵¶¶ Not found to be reported in databases.
IHC, immunohistochemical analysis; LOVD, Leiden Open Variation Database (http://www.insight-group.org/mutations/); mut+, mutation carriers; ND, not done.