Cancer and Germline mutations have implied impacts on functional structural elements.A, table of VUS, with EA >80 calculated based on HsASCC1 Isoform 1 (Iso1) with corresponding residues in Iso2 and ApASCC1 and colored according to functional impact. B, VUS positions mapped onto ApASCC1Δ40 structure (black sphere). C, Barrett’s oesophagus/osephageal adenocarcinoma germline site mutation (Asn290Ser), mapped onto ActSite-loop on HsASCC1Δ133 structure, likely disrupts ActSite-loop coordination to His179.