The c.776C>A sequence variant is predicted to introduce a premature stop codon and result in loss of function as a result of degradation of the mutated transcript by mRNA-surveillance mechanisms; however, because of a lack of patient material, we have been unable to confirm whether a truncated protein (lacking the C-terminal amino acids 259–436) is produced. In contrast, the in-frame c.714_731dup mutation is likely to result in the insertion of six amino acids (Met-Trp-Ser-Val-Leu-Gln) into the full-length kaptin. In order to investigate the functional outcome of this mutation, we undertook in silico analysis of the secondary structural elements of wild-type and altered kaptin. This revealed that the N-terminal half of kaptin is likely to comprise a series of relatively densely organized β sheets, interspersed by only three α helices, and becomes more α-helical starting with α-helix 4 (spanning amino acids 234–245; Figure 3A). Sequence and predicted structural conservation of both the N-terminal and C-terminal portions of kaptin are very high even between evolutionarily distant mammalian species (Figure S2). Strikingly, duplication of the six amino acids (241–246) is predicted to disrupt α-helix 4 and result in its conversion into an extended β sheet (Figure 3C) and is therefore likely to have a profound effect on kaptin function.