Your coverage estimate sounds about right, and this experimental design is one that I bet is ongoing in several labs right now as NGS moves to replace Sanger methods in the clinical arena. How to validate whole exome sequencing and comparing head-to-head with Sanger is a hot topic. One issue -- as you've alluded to with your 2 uncovered exons -- is how to fill the gaps not covered by exome seq -- designing Sanger "band-aids" to cover these areas does feel like a bit of a nuisance.
As for controls, you will need mutation-negative controls to prove that variants introduced by NGS are recognized by your informatics pipeline and not carried through to final results. You will also need a blinded cohort of mutation-positives and mutation-negatives (unknowns) to prove you can identify them correctly. All of the NGS results will need to be redone by Sanger methods to show validity of NGS compared to "gold-standard" current methods.
I encourage you to consult with friends/colleagues in pure clinical labs to design the best validation techniques, following CLIA guidelines as much as possible.
I would argue all of the NGS work should be done in one institutions, as there are likely to be artifacts introduced that are lab and machine-specific.
A version-tracking workflow tool for your informatics such as Galaxy is a must, and your reviewers will thank you.
A recent review that covers some of these issues is here.
