Table B.
Pathogenic Missense Mutations Found in the hMLH1 Gene[Note]
| Exon | ORF Position | ESE | Exonic Position | Initial Nucleotide | Mutated Nucleotide | Initial Amino Acid | Mutated Amino Acid | Type of Amino Acid Substitutiona | Family ID | Reference |
| 1 | 69 | 0 | 69 | A | T | Glu | Asp | C | … | Myriad et al. |
| 1 | 73 | 0 | 73 | A | T | Ile | Phe | R | 166 | W. Weber and M. Rodriguez-Bigas (unpublished) |
| 1 | 74 | 0 | 74 | T | C | Ile | Thr | R | 40547 | G. Norbury et al. (unpublished) |
| 1 | 83 | 1 | 83 | C | T | Pro | Leu | R | 52 | Wehner et al., Hum Mut 10:241–244 (1997) |
| 1 | 85 | 0 | 85 | G | T | Ala | Ser | C | … | Myriad et al. |
| 1 | 104 | 0 | 104 | T | G | Met | Arg | C | 3 | Tannergard et al., Cancer Res 55:6092–6096 (1995) |
| 1 | 116 | 0 | 116 | G | A | Cys | Ter | R | MDACC3014 | MDACC |
| 2 | 184 | 1 | 68 | C | A | Gln | Lys | C | 498 | Wehner et al., Hum Mut 10:241–244 (1997) |
| 2 | 191 | 1 | 75 | A | G | Asm | Ser | C | 2104 | J. T. Wijnen et al. (unpublished) |
| 2 | 199 | 1 | 83 | G | A | Gly | Arg | C | MDACC3011 | MDACC |
| 2 | 199 | 1 | 83 | G | A | Gly | Arg | C | MDACC3202 | MDACC |
| 2 | 199 | 1 | 83 | G | A | Gly | Arg | C | 304 | Tannergard et al., Cancer Res 55:6092–6096 (1995) |
| 2 | 199 | 1 | 83 | G | A | Gly | Arg | C | 1652 | Tannergard et al., Cancer Res 55:6092–6096 (1995) |
| 2 | 199 | 1 | 83 | G | A | Gly | Arg | C | 68 | Heinimann et al., Cancer 85 (12):2512–2518 (1999) |
| 2 | 199 | 1 | 83 | G | A | Gly | Arg | C | JPN-28 | Sasaki et al., Hum Mut 9:164 (1977} |
| 2 | 199 | 1 | 83 | G | A | Gly | Arg | C | MFI | Herfarth et al., Genes Chrom Cancer 18:42 (1997) |
| 2 | 199 | 1 | 83 | G | A | Gly | Arg | C | VSO15 | Hutter et al., Int J Cancer 78:680–684 (1998) |
| 2 | 200 | 1 | 84 | G | A | Gly | Glu | R | MDACC413075 | MDACC |
| 2 | 200 | 1 | 84 | G | A | Gly | Glu | R | MDACC380548 | MDACC |
| 2 | 203 | 0 | 87 | T | A | Ile | Asn | R | 18 | Tannergard et al., Cancer Res 55:6092–6096 (1995) |
| 3 | 230 | 0 | 23 | G | A | Cys | Tyr | R | IMS2 | S. E. Bennet (unpublished) |
| 3 | 250 | 0 | 43 | A | G | Lys | Glu | R | 171 | Lamberti et al., Gut 44:839–843 (1999) |
| 3 | 277 | 0 | 70 | A | G | Ser | Gly | R | 1 | Quaresima et al., Hum Mut 12; 433 (1998) |
| 3 | 299 | 1 | 92 | G | C | Arg | Pro | C | … | Myriad et al. |
| 3 | 304 | 1 | 97 | G | A | Glu | Lys | R | 61 | |
| 3 | 306 | 1 | 99 | G | T | Glu | Asp | R | … | Myriad et al. |
| 4 | 320 | 1 | 14 | T | G | Ile | Arg | R | 28/51/67 | Nyström-Lahti et al., Hum Mol Genet 5:763–769 (1996) |
| 4 | 350 | 1 | 44 | C | T | Thr | Met | R | … | A. M. Deffenbaugh et al. (unpublished) |
| 4 | 350 | 1 | 44 | C | T | Thr | Met | R | 431 | Krpelova (unpublished) |
| 4 | 350 | 1 | 44 | C | T | Thr | Met | R | S.B.-2575 | Stachow-Kurzawski (unpublished) |
| 4 | 350 | 1 | 44 | C | T | Thr | Met | R | 26 | Raedle et al. Gastro 116:A-489 (1999) |
| 4 | 350 | 1 | 44 | C | T | Thr | Met | R | LG | Liu et al., Nature Med 2:169–174 (1996) |
| 4 | 350 | 1 | 44 | C | T | Thr | Met | R | h83 | D. J. Bunyan (unpublished) |
| 4 | 350 | 1 | 44 | C | T | Thr | Met | R | BES-SG624 | B. Bressac-de Paillerets (unpublished) |
| 4 | 350 | 1 | 44 | C | T | Thr | Met | R | 84 | A. de la Chapelle (unpublished) |
| 4 | 350 | 1 | 44 | C | T | Thr | Met | R | 5 | Maliaka et al., Hum Genet 97:251–255 (1996) |
| 4 | 350 | 1 | 44 | C | T | Thr | Met | R | 434 | Buerstedde et al., J Med Genet 32:909–912 (1995) |
| 4 | 350 | 1 | 44 | C | G | Thr | Arg | C | … | Myriad et al. |
| 5 | 382 | 1 | 3 | G | C | Ala | Pro | C | 338 | V. Pensotti et al. (unpublished) |
| 6 | 479 | 1 | 25 | C | T | Ala | Val | R | … | A. M. Deffenbaugh et al. (unpublished) |
| 7 | 554 | 0 | 9 | T | G | Val | Gly | R | OZ-1 | A. M. Deffenbaugh et al. (unpublished) |
| 7 | 554 | 0 | 9 | T | G | Val | Gly | R | … | Kohonen-Corish et al., Am J Hum Genet 59:818–824 (1996) |
| 7 | 577 | 0 | 32 | T | C | Ser | Pro | C | NA-G.C. | P. Izzo et al. (unpublished) |
| 8 | 595 | 0 | 7 | G | C | Glu | Gln | R | 34 | T. Liu et al. (unpublished) |
| 8 | 637 | 0 | 49 | G | A | Val | Met | C | 39356 | Myriad et al. |
| 8 | 637 | 0 | 49 | G | A | Val | Met | C | … | Myriad et al. |
| 8 | 637 | 0 | 49 | G | A | Val | Met | C | … | G. Norbury et al. (unpublished) |
| 8 | 637 | 0 | 49 | G | A | Val | Met | C | … | Myriad et al. |
| 8 | 649 | 0 | 61 | C | T | Arg | Cys | R | 9 | Miyaki et al., J Mol Med 73:515–520 (1995) |
| 8 | 649 | 0 | 61 | C | T | Arg | Cys | R | SNU-H1006 | Han et al., J Natl Cancer Inst 88:1317–1319 (1996) |
| 8 | 677 | 1 | 89 | G | A | Arg | Gln | R | … | A. M. Deffenbaugh et al. (unpublished) |
| 8 | 677 | 1 | 89 | G | A | Arg | Gln | C | 6 | Maliaka et al., Hum Genet 97:251–255 (1996) |
| 8 | 677 | 1 | 89 | G | A | Arg | Gln | R | NLH-20 | Wijnen et al., Am J Hum Genet 58:300–307 (1996) |
| 9 | 731 | 1 | 55 | G | A | Gly | Asp | R | 311 | V. Pensotti et al. (unpublished) |
| 10 | 791 | 0 | 1 | A | G | Arg | Asp | R | 333633 | G. Norbury et al. (unpublished) |
| 10 | 793 | 1 | 3 | C | T | Arg | CyS | R | 198 | P. Hutter (unpublished) (1999) |
| 10 | 793 | 1 | 3 | C | T | Arg | CyS | R | VD0004 | T. Liu et al. (unpublished) |
| 10 | 794 | 1 | 4 | G | A | Arg | His | C | A-PD1 | Viel et al., Genes Chromosomes Cancer 18:8–18 (1997) |
| 10 | 803 | 0 | 13 | A | G | Glu | Gly | R | 80 | Liu et al., Clin Genet 53:131–135 (1998) |
| 10 | 814 | 0 | 24 | T | G | Leo | Val | R | … | Myriad et al. |
| 10 | 842 | 1 | 52 | C | T | Ala | Val | R | … | A. M. Deffenbaugh et al. (unpublished) |
| 11 | 977 | 1 | 94 | T | C | Val | Ala | R | 3273 | Myriad et al. |
| 11 | 977 | 1 | 94 | T | C | Val | Ala | R | 1515 | Liu et al., Nature Med 2:169–174 (1996) |
| 11 | 977 | 1 | 94 | T | C | Val | Ala | R | … | Buerstedde et al., J Med Genet 32:909–912 (1995) |
| 11 | 986 | 1 | 103 | A | C | His | Pro | C | 96 | Lamberti et al., Gut 44:839–843 (1999) |
| 12 | 1166 | 1 | 129 | G | A | Arg | Gln | C | … | A. M. Deffenbaugh et al. |
| 12 | 1217 | 0 | 180 | G | A | Ser | Asn | C | 209 | Cunningham et al., Am J Hum Genet 69:780–790 (2001) |
| 12 | 1321 | 1 | 284 | G | A | Ala | Thr | R | 466 | Cunningham et al., Am J Hum Genet 69:780–790 (2001) |
| 12 | 1321 | 1 | 284 | G | A | Ala | Thr | R | … | A. Krepelova (unpublished) |
| 13 | 1421 | 0 | 13 | G | A | Arg | Gln | R | DES-SG407 | B. Bressac-de Paillerets (unpublished) |
| 13 | 1474 | 1 | 66 | G | A | Ala | Thr | R | A4T | Möslein et al., Hum Mol Genet 5:1245–1252 (1996) |
| 13 | 1517 | 0 | 109 | T | C | Val | Ala | R | 3118 | Liu et al., Nature Med 2:169–174 (1996) |
| 13 | 1517 | 0 | 109 | T | C | Val | Ala | R | MDACC387858 | MDACC |
| 13 | 1517 | 0 | 109 | T | C | Val | Ala | R | … | A. M. Deffenbaugh et al. (unpublished) |
| 14 | 1569 | 0 | 12 | G | T | Glu | Asp | R | … | Myriad et al. |
| 14 | 1625 | 1 | 68 | A | T | Gln | Leu | R | SNUH-H2 | Han et al., Hum Mol Genet 4:237–242 (1995) |
| 14 | 1646 | 0 | 89 | T | C | Leo | Pro | R | SNU-H14 | Han et al., J. Natl. Cancer Inst. 88:1317–1319 (1996) |
| 14 | 1652 | 1 | 95 | A | T | Asp | Thr | R | VS012 | Hutter et al., Int J Cancer 78:680–684 (1998) |
| 15 | 1693 | 0 | 27 | A | T | Ile | Phe | R | VD001 | Hutter et al., Int J Cancer 78:680–684 (1998) |
| 15 | 1721 | 1 | 55 | T | C | Leo | Pro | R | SNUH-H1 | Han et al., Hum Mol Genet 4:237–242 (1995) |
| 16 | 1733 | 0 | 2 | A | G | Glu | Gly | R | 21 | A. de la Chapelle et al. (unpublished) |
| 16 | 1744 | 0 | 13 | C | G | Leu | Val | C | JPN-1 | Han et al., Hum Mol Genet 4:237–242 (1995) |
| 16 | 1771 | 0 | 40 | A | G | Glu | Gly | R | END0003 | Hutter et al., Int J Cancer 78:680–684 (1998) |
| 16 | 1853 | 0 | 122 | A | C | Lys | Thr | R | US-6 | T. Caldes (unpublished) |
| 17 | 1958 | 1 | 62 | T | G | Leu | Arg | R | … | Han et al., Hum Mol Genet 14:237–242 (1995) |
| 17 | 1961 | 1 | 65 | C | T | Pro | Leu | R | 38469 | G. Norbury et al. (unpublished) |
| 17 | 1963 | 1 | 67 | A | G | Ile | Val | C | … | Myriad et al. |
| 17 | 1976 | 1 | 80 | G | C | Arg | Pro | C | NL56 | Nyström-Lahti et al., Hum Mol Genet 5:763–769 (1996) |
| 17 | 1976 | 1 | 80 | G | C | Arg | Pro | C | 7 | A. de la Chapelle et al. (unpublished) (also mut. MLH1 exon 16, codon 618) |
| 17 | 1976 | 1 | 80 | G | A | Arg | Gla | C | 51 | J. T. Wijnen et al. (unpublished) |
| 17 | 1988 | 1 | 92 | A | G | Glu | Gly | R | CHI-SG277 | B. Bressac-de Paillerets (unpublished) |
| 18 | 2027 | 0 | 38 | T | G | Leu | Arg | R | … | Myriad et al. |
| 18 | 2041 | 0 | 52 | G | A | Ala | Thr | R | CO10 | Kurzawska and G. Kurzawski (unpublished) |
| 18 | 2041 | 0 | 52 | G | A | Ala | Thr | R | B.T.-1881 | Froggatt et al., J. Med. Genet.33: 726–730 (1996) |
| 19 | 2146 | 1 | 44 | G | A | Val | Meth | C | GE111 | Myriad et al. |
| 19 | 2146 | 1 | 44 | G | A | Val | Meth | C | … | Hutter et al., Int J Cancer 78:680–684 (1998) |
| 19 | 2152 | 0 | 50 | C | T | His | Tyr | R | CHO-SG632 | D. J. Bunyan (unpublished) |
Note.— The table enlists missense mutations from the HNPCC mutation database (accessed March 2003) and mutation data obtained by M.L.F. at MDACC.
a
C = conservative; R = radical.