However, high tumor DNA levels (including high ctDNA shedding, i.e., high TF) or allelic imbalance due to loss of heterozygosity or copy number variation can cause somatic variants to occur in similar VAF ranges as germline variants, such that definitive characterization of a variant as somatic versus germline is not possible using VAF alone [[82], [83], [84]]. The gene discussed is TF; the disease is neoplasm.