Haematological malignancies cancer susceptibility

Gene: POT1

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.

Created: 12 Mar 2026, 9:51 a.m. | Last Modified: 12 Mar 2026, 9:51 a.m.

Panel Version: 4.39

Comment on phenotypes: OMIM phenotypes (Tumor predisposition syndrome 3, OMIM:615848) accessed on 27-10-2025

Created: 28 Oct 2025, 9:46 a.m. | Last Modified: 28 Oct 2025, 9:46 a.m.

Panel Version: 4.34

Comment on list classification: Multiple studies have been published showing germline POT1 variants predispose to a broad spectrum of haematological cancers including chronic lymphocytic leukaemia, lymphomas and myeloid malignancies. Inclusion on this panel may be warranted to allow clinical surveillance of high-risk families.

However, haematologic malignancies often occur as part of a broader spectrum of POT1-associated cancers and therefore this gene will be flagged for additional GMS expert review to determine whether it is appropriate to include on this panel.

Created: 27 Oct 2025, 2:50 p.m. | Last Modified: 27 Oct 2025, 2:50 p.m.

Panel Version: 4.32

Germline variants in POT1 have been linked to a wide range of haematological malignancies including myeloid and lymphoid neoplasms (PMID: 27528712; 29693246; 33216348; 34193977; 34769003) and multiple myeloma (PMID: 36467798; 39845416). POT1 variants lead to telomeric elongation and increased telomere fragility as the main functional effect.

Created: 27 Oct 2025, 2:41 p.m. | Last Modified: 27 Oct 2025, 2:52 p.m.

Panel Version: 4.32

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Tumor predisposition syndrome 3, OMIM:615848; Lymphoid and myeloid cancers; Multiple myeloma

Publications

• 27528712
• 29693246
• 33216348
• 34193977
• 34769003
• 36467798
• 39845416

Green List (high evidence)