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Non-synonymous mutations frequently change the structure or function of proteins, which may affect immunological and metabolic processes 56,57

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Intrinsic (mitochondrial) pathways are also activated, with pro-apoptotic Bcl-2 family members (Bid, Bak, Bax) promoting mitochondrial outer membrane permeabilization, cytochrome C release, and apoptosome formation (cytochrome C + APAF-1 + procaspase-9)