How did I miss this?!?
open the door by taking all the "normal variation" and deleterious mutations and put them into nice protein .FASTA databases for us. Then we just do what we'd normally do, maybe mumble something semi-coherent about FDR in the method section of our paper and we're done.
If you're in the cancer realm, we've had a great tool like this for years now. The XMAN database is a composite of hundreds of thousands of mutations that we can use for searches if we've got enough processing power, or we can reduce them and utilize them.
After using it nonstop for years it's honestly pretty depressing to work with other diseases that don't have a resource like this.
How do you improve on something this useful? Well...you could start by adding a few million more mutated sequences.
A. FEW. MILLION. MORE.