While mutations such as deletions, frameshifts, and nonsense mutations generate truncated proteins, missense mutations often lead to unstable proteins as judged by immunofluorescence microscopy.
These mutations found on APC are usually nonsense or frame shift mutations, which generate truncated forms of APC.
In fact, mutations of PRDM1 have been clarified in NK92 cells and some cases of EN-NK/T-NT, in which base-substitution in Exon 5 (C951A) or Exon 4 (C864A) results in nonsense mutation to generate truncated PRDM1 [ 7].
Four of these ZFP57 mutations (E106VfsX28, C261X, G299fsX1 and G461GfsX17) generate truncated forms of the protein and three (R248H, H277N and H458D) are missense mutations affecting residues highly conserved among several mammalian species (see Fig. 1).
Ninety percent of the identified NF2 mutations are frameshift, nonsense, and splice alterations predicted to generate truncated merlin proteins.
Recombined Nrg1flox alleles generate truncated Nrg1 mRNAs lacking a functional EGF domain (Yang et al, 2001).
These would generate truncated or aberrant proteins whose role remains unknown.
Overall, the presence of the missense pathogenic mutations in sr1, sr2, srX, or sr3 established on average a set of phenotypes (i.e., SPAX scores) significantly less severe (i.e., lower) than those observed for mutations that generated truncated proteins (ANOVA PP < 0.0001).
Frameshift mutations affecting coding repetitive sequences are among the most common mutations occurring in MSI cancers, as a consequence of DNA polymerase slippage, frequently generating truncated proteins (2).
Furthermore, six novel mutations in FHL-1 have been directly linked with the development of HCM, by generating truncated or deleterious FHL-1 proteins.
