Activating HER2 mutations are very rare [11].
However, several single-nucleotide polymorphisms
(SNPs) have been identified and two have been extensively
studied in relation to breast cancer. One SNP
corresponds to a residue in the transmembrane region at
codon 655 [12] and encodes either isoleucine (Ile; ATC)
or valine (Val; GTC). This SNP is near to sites of mutation
in the rat neu homologue (Val664Glu), within a
consensus sequence that induces transmembrane helix
dimerisation. In a model derived by a computational
method [13], a Val residue at codon 655 (as opposed to
Ile) would stabilise the formation of active dimers of
HER2.