A subset of the sequence variants is predicted to introduce a premature termination codon and hence truncate the wild-type protein sequence. Truncating variants are usually highly deleterious to protein function: they constitute a substantial proportion of monogenic (mendelian) disease-causing mutations but a relatively small proportion of polymorphisms. Therefore, as the first analytic step to identify new genes involved in mental retardation, we considered the set of truncating variants detected in the screen.
