A novel TERT variant associated with a telomere biology disorder and challenges in variant classification

EJHaem. 2025 Jan 24;6(1):e1066. doi: 10.1002/jha2.1066. eCollection 2025 Feb.

Abstract

Telomere biology disorders (TBDs) are inherited conditions associated with multisystem manifestations. We describe clinical and functional characterisation of a novel TERT variant. Whole-genome sequencing was performed along with single telomere length analysis (STELA). Telomerase activity and processivity were assessed. A novel TERT variant (K710R) was detected in a patient with classic TBD features showing reduced telomerase activity and processivity. Despite clinical and functional evidence, the variant was classified as a variant of uncertain significance. We have described a novel TERT variant and highlighted the need for further refinement of variant classification specific for TBDs.

Keywords: TERT variant; genetic anticipation; telomerase activity; telomere biology disorders; variant curation.