Table 2.
Short Variant Alterations Observed in ERBB2‐Mutated and ERBB3‐Mutated mCRC
| ERBB2 | ||||
|---|---|---|---|---|
| Mutation Type | Alteration | Count | Cases With Multiple Alterations | |
| SV Only | Amplification | |||
| Missense | N=181 | |||
| ECD | ||||
| P122L | 1 | |||
| E265K | 1 | |||
| G292R | 1 | |||
| S310F | 19 | 6 | ||
| S310Y | 8 | 1 | 1 | |
| L313V | 1 | |||
| TM | ||||
| V659E | 1 | 1 | ||
| G660D | 2 | 1 | ||
| S653C | 1 | 1 | ||
| JM | ||||
| R678Q | 44 | 1 | 3 | |
| KD | ||||
| T733I | 1 | 1 | ||
| L755S | 12 | 3 | 1 | |
| I767M | 2 | |||
| D769H | 1 | |||
| D769N | 2 | |||
| D769Y | 6 | 3 | 1 | |
| V773M | 2 | |||
| G776S | 1 | 1 | ||
| G776V | 6 | |||
| V777L | 19 | 2 | 9 | |
| V777M | 4 | |||
| V842I | 31 | 4 | 2 | |
| T862A | 11 | 1 | 2 | |
| H878Y | 2 | 1 | ||
| R896C | 1 | |||
| R896H | 1 | |||
| Truncationa | N=5 | |||
| A1232fs*25+ | 2 | 1 | ||
| G1189fs*9 | 1 | |||
| P1170fs*88+ | 1 | |||
| Q1136fs*5 | 1 | |||
| Indel | N=1 | |||
| P780_Y781insGSP | 1 | |||
| Deletion exon 16 | N=2 | |||
| Splice site 1899‐59_1945del106 | 1 | |||
| Deletion exon 16 | 1 | |||
| ERBB3 | ||||
|---|---|---|---|---|
| Mutation Type | Alteration | Count | Cases with Multiple SV | |
| Missense | N=154 | |||
| ECD | ||||
| M60K | 7 | 1 | ||
| M91I | 1 | |||
| R103H | 2 | 1 | ||
| V104L | 17 | |||
| V104M | 35 | 2 | ||
| N126K | 1 | |||
| A232V | 17 | 2 | ||
| A245V | 2 | |||
| R258H | 2 | |||
| G284R | 26 | 1 | ||
| D297Y | 14 | |||
| K329E | 4 | |||
| E332K | 3 | |||
| T355A | 1 | |||
| T355I | 1 | 1 | ||
| Y464C | 1 | |||
| G582V | 1 | 1 | ||
| KD | N=13 | |||
| S846I | 5 | 1 | ||
| E928G | 8 | 2 | ||
| Other | N=5 | |||
| A1023T | 1 | 1 | ||
| S1049G | 1 | |||
| P1212S | 3 | |||
Abbreviations: ECD, extracellular domain; JM, juxtamembrane region; KD, kinase domain; mCRC, metastatic colorectal cancer; SV, short variant; TM, transmembrane domain.
a
Frameshift alterations are as follows: first amino acid and position changed, fs* to note variant type and termination codon, position of termination codon relative to first amino acid changed. A plus sign (+) indicates that no termination codon was observed in the new frame before the end of the original coding sequence.