Analysis of tumour (including circulating tumour) DNA may identify variants of possible germline origin, but determining which findings warrant germline follow-up is challenging. We present a framework to guide follow-up of variants of putative germline origin identified through testing of tissue/circulating tumour DNA, giving due consideration to clinical/public health utility, germline conversion rates and variant-specific reporting guidance, harmonised with NHS-specific policy and relevant guidance from other UK professional bodies. This framework supports consistent, clinically meaningful germline follow-up while avoiding unnecessary testing and supporting sustainable use of genomic services.
Sequencing of tumour-derived DNA from solid and liquid biopsies (ctDNA) is now widely used in UK oncology practice, with the primary purpose of identifying somatic variants that inform diagnosis, prognosis or treatment decision-making.