The invention provides methods for determining the mutation burden of a tumor by assaying tumor DNA that is representative of genetic loci that are themselves representative of genetics of the tumor. The assayed tumor DNA may be itself agnostic as to loci, so long as it is representative of loci that are representative of tumor mutation burden. The invention provides for assays in which the tumor DNA being sequenced or tested can be something other than, and possibly less than, a full panel of oncogenes that is expected to stand for a tumor's mutational load.