I came across this paper while looking for some HCV genome linkage studies: Comparative analysis of nearly full-length hepatitis C virus quasispecies from patients experiencing viral breakthrough during antiviral therapy: clustered mutations in three functional genes, E2, NS2, and NS5a
This shows that there are some PAIRS of mutations which lead to viral breakthroughs but the single mutations have no noticeable effect. They use a different reference strain so their positions aren't immediately comparable to mine but I have checked and their reference is in my alignments ... so I'll just need to do a simple conversion to check it out.
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