Pilar Mur and colleagues report a study on the coding region and exon-intron boundaries of UNC5C gene in 544 familial colorectal cancer (CRC) or polyposis patients, using and massively parallel sequencing. They identified 8 novel or rare variants, all missense, in eight families but they showed that 7 of the 8 identified variants were not are not consistent with a causal effect (including c.1882_1883delinsAA (p.A628K)) and one variant, c.2210G>A (p.S737N), remained unclassified.