Table 1.
RET Proto-Oncogene Sequence Variation
| RET exon | Codon | Codon sequence change* | Amino acid change | References |
|---|---|---|---|---|
| 10 | 603 | AAA → CAA | K603Q | 20 |
| 609 | TGC → AGC† | C609S | 3 | |
| TGC → CGC | C609R | 3, 20, 24 | ||
| TGC → GGC | C609G | 3, 20 | ||
| • TGC → TAC | C609Y | 3, 20, 24 | ||
| • TGC → TCC | C609S | 3, 20 | ||
| TGC → TTC | C609F | 3 | ||
| TGC → TGG† | C609W | 3, 20, 38 | ||
| 611 | TGC → AGC | C611S | 3, 20 | |
| • TGC → CGC | C611R | 3, 20 | ||
| TGC → GGC | C611G | 3, 20, 24 | ||
| • TGC → TAC | C611Y | 3, 20, 24 | ||
| TGC → TCC† | C611S | 3 | ||
| • TGC → TTC | C611F | 3, 20 | ||
| TGC → TGG | C611W | 3, 20, 24 | ||
| 618 | TGC → AGC | C618S | 3, 20, 24 | |
| • TGC → CGC | C618R | 3, 20, 24 | ||
| • TGC → GGC | C618G | 3, 20, 24 | ||
| • TGC → TAC | C618Y | 3, 20, 24 | ||
| • TGC → TCC | C618S | 3, 20, 24 | ||
| • TGC → TTC | C618F | 3, 20, 24 | ||
| TGC → TGG | C618W | 3 | ||
| 620 | • TGC → AGC | C620S | 3, 20 | |
| TGC → CGC | C620R | 3, 20, 24 | ||
| TGC → GGC | C620G | 3, 20, 24 | ||
| • TGC → TAC | C620Y | 3, 20, 24 | ||
| • TGC → TCC | C620S | 3, 20, 24 | ||
| • TGC → TTC | C620F | 3, 20, 24 | ||
| • TGC → TGG | C620W | 3, 20 | ||
| 11 | 630 | TGC → CGC | C630R | 3 |
| TGC → TAC | C630Y | 3, 20 | ||
| TGC → TTC | C630F | 3, 20, 24 | ||
| TGC → TCC | C630S | 3, 20 | ||
| 631 | • GAC → GAT† | D631D | 3 | |
| GAC → TAC† | D631Y | 3 | ||
| GAC → GAA† | D631E | 3, 34 | ||
| GAC → GTC† | D631V | 3, 34 | ||
| 634 | • TGC → AGC | C634S | 3, 20, 24 | |
| • TGC → CGC | C634R | 3, 20, 24 | ||
| • TGC → GGC | C634G | 3, 20, 24 | ||
| • TGC → TAC | C634Y | 3, 20, 24 | ||
| • TGC → TCC | C634S | 3, 20, 24 | ||
| • TGC → TTC | C634F | 3, 20, 24 | ||
| • TGC → TGG | C634W | 3, 20, 24 | ||
| 640 | GCC → GGC | A640G | 20 | |
| 13 | 768 | • GAG → GAC | E768D | 3, 20, 24 |
| GAG → GAT | E768D | 3, 20 | ||
| 769 | • CTT → CTG‡ | L769L | 2, 19, 20 | |
| 778 | GTC → ATC | V778I | 20 | |
| 781 | CAG → CGG | Q781R | 20 | |
| 790 | TTG → TTT | L790F | 20, 24, 28 | |
| TTG → TTC | L790F | 20, 24, 28 | ||
| 791 | TAT → TTT | Y791F | 24, 27, 28 | |
| 14 | 804 | • GTG → ATG | V804M | 3, 20, 24 |
| • GTG → TTG | V804L | 3, 20, 24 | ||
| GTG → CTG | V804L | 3 | ||
| 806 | TAC → TGC§ | Y806C | 24, 35 | |
| 844 | CGG → CTG | R844L | 20, 24 | |
| 852 | ATC → ATG† | I852M | 20, 29 | |
| 16 | 912 | CGG → CCG | R912P | 30 |
| 918 | • ATG → ACG | M918T | 3, 20, 24 | |
| 922 | TCC → TAC† | S922Y | 20, 31 |
*
Sequence variation is heterozygous unless otherwise stated in the text. Codon DNA sequence is listed with the nucleotide of change in bold for mutations and underlined for polymorphisms/sequence variants. •, available RET sequence variation samples.
†
Rare sequence variants of unknown significance or not causative of MEN2 syndromes; see references. Three variants in codons 609 or 611 are within RET pathogenic codons yet are not associated with MEN2 syndromes. Variants at codons 922 and 852 were previously found in MTC patients, yet may not be causative of MEN2 syndromes.
‡
Benign polymorphism, 0.26 allelic frequency.
§
806 is only pathogenic with 804 mutation on same allele.