Diagnostic Clinical Genome and Exome Sequencing

In “Diagnostic Clinical Genome and Exome Sequencing”, Biesecker et al. are critical of the way doctors have been ordering CGES tests in the past and offer new factors for a doctor to consider before ordering the CGES test. They define the basics of CGES testing and suggest various measures that should be taken prior to placing an order for CGES.
In what situations would sequencing be a logical order to make? What factors need to be known before a call is made? Furthermore, what needs to be known before a variant can be labelled caustic?