Many genetic diseases are caused by mutations in a gene and often, it is a single nucleotide polymorphism (SNP) that has dramatic consequences (e.g. the E6V hemoglobin mutation in sickle cell disease). Other diseases are the result of multiple mutations, that have occurred within various genes (often in cancer).
My question is, are there also many (or any?) known diseases that only manifest if two or more particular mutations arise in the same gene? My assumption is that they exist, but are rather rare; an ideal answer would point me to a publication with quantitative data: how many known diseases are caused by a single mutation, how many by double, etc.
Regarding alleles: I am not asking whether mutations have to occur homozygously to manifest; I'm talking about mutations in the same copy of the gene; for coding sequences, we would be talking about a double (triple,...) mutant of a protein.