Annotation Detail

Information
Associated Genes
TP53
Associated Variants
TP53 p.Arg248Gln (p.R248Q) ( ENST00000604348.6, ENST00000504937.5, ENST00000269305.9, ENST00000576024.2, ENST00000420246.6, ENST00000510385.5, ENST00000504290.5, ENST00000610538.4, ENST00000445888.6, ENST00000455263.6, ENST00000359597.8, ENST00000413465.6, ENST00000610292.4, ENST00000610623.4, ENST00000618944.4, ENST00000619186.4, ENST00000619485.4, ENST00000620739.4, ENST00000622645.4, ENST00000714356.1, ENST00000714357.1, ENST00000714359.1, ENST00000714408.1, ENST00000714409.1 )
TP53 p.Arg248Gln (p.R248Q) ( ENST00000269305.9, ENST00000359597.8, ENST00000413465.6, ENST00000420246.6, ENST00000445888.6, ENST00000455263.6, ENST00000504290.5, ENST00000504937.5, ENST00000510385.5, ENST00000576024.2, ENST00000604348.6, ENST00000610292.4, ENST00000610538.4, ENST00000610623.4, ENST00000618944.4, ENST00000619186.4, ENST00000619485.4, ENST00000620739.4, ENST00000622645.4, ENST00000714356.1, ENST00000714357.1, ENST00000714359.1, ENST00000714408.1, ENST00000714409.1 )
Associated Disease
lymphoma
Source Database
CIViC Evidence
Description
In mouse models, the R248Q variant had accelerated onset of all tumor types and accelerated death rate. Endogenous R248Q proteins are devoid of several important wildtype tp53 tumor-suppressor functions including transcription of cell cycle arrest genes, replicative senescence and irradiation-induced apoptosis. Patients with germline R248Q/+ genotype showed a drastically younger median age until first tumor onset compared with patients with a null/+ genotype (19.5 vs 30 years, P=0.023).
Variant Origin
germline
Variant Origin
Rare Germline
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/7161
Gene URL
https://civic.genome.wustl.edu/links/genes/45
Variant URL
https://civic.genome.wustl.edu/links/variants/117
Rating
4
Evidence Type
Predisposing
Disease
Lymphoma
Evidence Direction
Supports
Evidence Level
D
Clinical Significance
Likely Pathogenic
Pubmed
23538418
Drugs