Table A.
Pathogenic Missense Mutations Found in the hMSH2 Gene[Note]
| Nucleotide Position in ORF | ESE | Exon | Codon | Nucleotide | Nucleotide Change | Consequence | Type of Amino Acid Substitutiona | Geographic Origin | Family ID | Reference |
| 4 | 0 | 1 | 2 | 4 | G→A | Ala→Thr | C | None specified | … | Myriad et al. |
| 182 | 1 | 1 | 61 | 182 | A→C | Gln→Pro | C | Western Europe | … | Myriad et al. |
| 308 | 1 | 2 | 103 | 308 | A→G | Tyr→Cys | R | None specified | … | Myriad et al. |
| 319 | 0 | 2 | 107 | 319 | G→C | Ala→Prol | C | Czech Republic | PT523 | A. Krepelova (unpublished) |
| 380 | 0 | 3 | 127 | 380 | A→G | Asn→Ser | C | None specified | … | Myriad et al. |
| 380 | 0 | 3 | 127 | 380 | A→G | Asn→Ser | C | Africa | … | Myriad et al. |
| 380 | 0 | 3 | 127 | 380 | A→G | Asn→Ser | C | Africa | … | Myriad et al. |
| 380 | 0 | 3 | 127 | 380 | A→G | Asn→Ser | C | None specified | … | Myriad et al. |
| 380 | 0 | 3 | 127 | 380 | A→G | Asn→Ser | C | None specified | … | Myriad et al. |
| 435 | 1 | 3 | 145 | 435 | T→G | Ile→Met | C | Czech Republic | Patient 338 | A. Krepelova (unpublished) |
| 435 | 1 | 3 | 145 | 435 | T→G | Ile→Met | C | None specified | … | A. M. Deffenbaugh et al. (unpublished) |
| 435 | 1 | 3 | 145 | 435 | T→G | Ile→Met | C | Western European | … | Myriad et al. |
| 446 | 0 | 3 | 149 | 446 | G→A | Gly→Asp | R | None specified | … | A. M. Deffenbaugh et al. (unpublished) |
| 505 | 1 | 3 | 169 | 505 | A→G | Ile→Valb | C | Asia | … | A. M. Deffenbaugh et al. (unpublished) |
| 593 | 1 | 3 | 198 | 593 | GAA→GGA | Glu→Gly | R | Sweden | 199 | Unpublished |
| 595 | 0 | 3 | 199 | 595 | T→C | Cys→Arg | R | Hong Kong | [Turcot] | Yuen et al., Am J Pathol 153:1181–1188 (1998) |
| 742 | 0 | 4 | 248 | 742 | A→G | Lys→Glu | C | Western Europe | … | Myriad et al. |
| 792 | 1 | 4 | 264 | 792 | G→C | Gln→His | R | Western Europe | … | Myriad et al. |
| 806 | 1 | 5 | 269 | 806 | C→T | Ser→Leu | R | Latin America/Caribbean | … | A. M. Deffenbaugh et al. (unpublished) |
| 815 | 1 | 5 | 272 | 815 | C→T | Ala→Val | C | None specified | 0108 | MDACCc |
| 913 | 1 | 5 | 305 | 913 | G→A | Ala→Thr | C | Netherlands | NL-38 | Wijnen et al. (unpublished) |
| 965 | 1 | 6 | 322 | 965 | G→Ab | Gly→Asp | C | Russia | 1 | Maliaka et al. Hum Genet 97:251–255 (1996) |
| 965 | 1 | 6 | 322 | 965 | G→Ab | Gly→Asp | C | Germany | 186 | Brieger et al. Clinical Chemistry 45: 1564–1567 (1999) |
| 965 | 1 | 6 | 322 | 965 | G→Ab | Gly→Asp | C | United States | 0205 | MDACCc |
| 997 | 0 | 6 | 333 | 997 | T→C | Cys→Arg | R | Nigeria | 114-I-OL | A. de la Chapelle et al. (unpublished) |
| 998 | 0 | 6 | 333 | 998 | G→A | Cys→Tyr | R | Australia | IMS5 | S. E. Bennett (unpublished) |
| 1012 | 1 | 6 | 338 | 1012 | G→A | Gly→Arg | R | None specified | … | A. M. Deffenbaugh et al. (unpublished) |
| 1082 | 0 | 7 | 361 | 1082 | A→G | Arg→Ser | R | Western Europe | … | Myriad et al. |
| 1319 | 1 | 8 | 440 | 1319 | T→C | Leu→Pro | R | Lithuania | O3 | E. Avizienyte et al. (unpublished) |
| 1508 | 0 | 9 | 503 | 1508 | T→C | Leu→Pro | R | None specified | … | Myriad et al. |
| 1516 | 1 | 10 | 506 | 1516 | G→T | Asp→Tyr | R | Korea | SNU-YC13 | Han et al., J. Natl. Cancer Inst. 88: 1317–1319 (1996) |
| 1571 | 1 | 10 | 524 | 1571 | G→C | Arg→Pro | R | None specified | Patient 2774 with ovarian cancer | Orth et al., Cold Spring Harbor Symp Quant Biol LIX: 349 (1994) |
| 1600 | 1 | 10 | 534 | 1600 | C→T | Arg→Cys | R | United States | 3080 | MDACCc |
| 1774 | 1 | 12 | 592 | 1774 | A→G | Met→Val | C | None specified | … | Myriad et al. |
| 1807 | 0 | 12 | 603 | 1807 | G→A | Asp→Asn | R | Finland | Patient 138 | Salovaara et al., J Clin Oncol 18: 2193–2200 (2000) |
| 1864 | 0 | 12 | 622 | 1864 | C→A | Missense | R | Argentina | CRE001 | Chialina et al. (unpublished) |
| 1865 | 0 | 12 | 622 | 1865 | C→T | Pro→Leu | R | New Zealand | J | Liu et al., Cancer Res. 54: 4590–4594 (1994) |
| 1906 | 1 | 12 | 636 | 1906 | G→Cb | Ala→Pro | C | France | CHI-S6351 | B. Bressac-de Paillerets, unpublished |
| 1906 | 1 | 12 | 636 | 1906 | G→Cb | Ala→Pro | C | United States | 54 | A. de la Chapelle (unpublished) |
| 1906 | 1 | 12 | 636 | 1906 | G→C | Ala→Pro | C | Ashkenazi Jewish | MONO7 (y) | Yuan et al. J Med Genet 36:790–793 (1999) |
| 1906 | 1 | 12 | 636 | 1906 | G→C | Ala→Pro | C | None specified | … | Myriad et al. |
| 2090 | 0 | 13 | 697 | 2090 | G→T | Cys→Phe | R | Germany | 56 | Raedle et al. Gastroenterology 116:489A (1999) |
| 2090 | 0 | 13 | 697 | 2090 | G→T | Cys→Phe | R | Germany | 62 | Wehner et al., Hum Mut 10:241–244 (1997) |
| 2164 | 1 | 13 | 722 | 2164 | G→A | Val→Ile | R | United States | 0024 | MDACCc |
| 2251 | 0 | 14 | 751 | 2251 | G→A | Gly→Arg | R | France | BIL-IGR1924 | B. Bressac-de Paillerets |
| 2500 | 0 | 15 | 834 | 2500 | G→A | Ala→Thr | C | Netherlands | NL57 | J. T. Wijnen et al. (unpublished) |
| 2714 | 1 | 16 | 905 | 2714 | C→G | Thr→Arg | R | United Kingdom | C015 | Froggatt et al., J. Med. Genet. 33:726–730 (1996) |
| 2714 | 1 | 16 | 905 | 2714 | C→T | Thr→Ile | R | Central/eastern Europe | … | Myriad et al. |
| 2790 | 0 | 16 | 930 | 2790 | A→Gb | Ile→Met | C | Spain | GE008 | P. Hutter (unpublished) (1999) |
Note.— The table enlists missense mutations from the HNPCC mutation database (accessed March 2003) and mutation data obtained by M.L.F. at The University of Texas M. D. Anderson Cancer Center (MDACC).
a
C = conservative; R = radical.
b
Of unknown pathogenicity.
c
The University of Texas M. D. Anderson Cancer Center.