Somatic vs germline mutation

Germline mutations are in the DNA you were born with — present in healthy and tumor tissue alike. Somatic mutations are acquired later, in a particular cell lineage; the ones that accumulate in a tumor are what make it genetically distinct from the patient's normal cells.

Neoantigens come (almost) exclusively from somatic mutations: because they're absent from healthy tissue, the immune system was never trained to tolerate them. The standard way to find them is to sequence both tumor and matched normal tissue and subtract — anything present only in the tumor is a somatic candidate. Germline variants are filtered out precisely because targeting them would mean attacking healthy cells.