Incidentalome

Gene: POT1

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Hereditary neoplastic syndrome, MONDO:0015356, POT1-related

Green List (high evidence)

CLL (PMID: 27528712, published 2016) identified 4 families with POT1 variants and CLL.
Aberrant splicing of intron 13 (chromosome 7 g.124481233C.T/c.1164-1G.A) confirmed by RT-PCR. Missense p.Tyr36Cys and p.Gln376Arg predicted to be pathogenic by in silico methods. p.Gln358SerfsTer13 predicted to cause premature truncation.

Hodgkin Lymphoma (PMID: 29693246, published 2018) identified 2 families with POT1 variants and Hodgkin lymphoma.
p.Asp224Asn in 4 carriers with Hodgkin lymphoma. Variant validated functionally.
p.Tryp26His in 2 carriers with Hodgkin lymphoma. Some functional validation performed.

AML (PMID: 34769003, published 2021) identified p.Q199* in a 8yo with AML and monosomy 7. Unaffected father, de novo status of variant not confirmed. Some functional validation (but conflicting).

Multiple myeloma (PMID: 36467798, published 2022) looked at inherited predisposition for multiple myeloma. Identified 4 families with POT1 variants who have myeloma, thyroid cancer, and AML. Functional validation not performed.

Multiple haematological malignancies, cutaneous melanoma and solid cancers in a family from Queensland (PMID: 33216348, published 2020). The variant p.D224N has been reported and functionally validated by other authors.

Cutaneous melanoma (PMID: 24686849; PMID:24686846, published in same issue of journal in 2014) identified families with strong family history of melanoma. PMID: 24686849 identified 4 families with 4 different POT1 variants. PMID 24686846 identified 5 families with same founder p.Ser270Asn variant. Functional validation of pathogenicity performed in the 2 papers.

Li-Fraumeni Like syndrome (PMID: 26403419 published 2015) identified 3 families with p.R117C variant and strong family history of Li-Fraumeni Like syndrome. Variant functionally validated.

Medullary thyroid cancer (PMID: 32492864 published 2020) identified 1 family with p.V29L. The variant segregates with papillary thyroid cancer. Some functional validation performed.
Sources: Expert list

Created: 1 Jun 2023, 1:03 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Tumour predisposition with variety of solid and haematological malignancies reported.

Publications

• (PMID:27528712
• PMID: 29693246
• PMID: 34769003
• PMID: 36467798
• PMID: 33216348
• PMID: 24686849
• PMID:24686846
• PMID: 26403419
• PMID: 32492864)