Li-Fraumeni syndrome (LFS) is an inherited, autosomal-dominant condition that 
predisposes individuals to a wide-spectrum of tumors at an early age. 
Approximately 70% of families with classic LFS have pathogenic variants in the 
tumor suppressor gene TP53 that disrupt protein function or stability. While 
more than 70% of pathogenic variants in TP53 are missense variants, the vast 
majority occur very infrequently, and thus their clinical significance is 
uncertain or conflicting. Here, we report an extremely rare TP53 missense 
variant, c.799C > T (p.Arg267Trp), identified in a 2-year-old Saudi proband 
diagnosed with choroid plexus carcinoma (CPC) and six of his first- and 
second-degree relatives. CPC is frequently found in families with LFS, and this 
is the first detailed report of a family with this variant. Intriguingly, the 
proband's father is homozygous for TP53 c.799C > T and phenotypically normal at 
39 years of age. While loss of TP53 heterozygosity is often observed in tumors 
from individuals with LFS, homozygous germline TP53 pathogenic variants are 
rare. Based on our analysis of this single family, we hypothesize that TP53 
c.799C > T has low or variable penetrance for LFS, with predisposition to the 
development of CPC. The observations from this family have furthered our 
understanding of the phenotypic variability that may be caused by one variant of 
TP53, even in the same family, and suggest that other factors (genetic and/or 
environmental) may play a role in mechanism of disease manifestation in LFS.