Annotation Detail

Information
Associated Genes
TP53
Associated Variants
TP53 p.Tyr220Cys (p.Y220C) ( ENST00000510385.5, ENST00000504937.5, ENST00000604348.6, ENST00000576024.2, ENST00000504290.5, ENST00000269305.9, ENST00000359597.8, ENST00000618944.4, ENST00000619186.4, ENST00000413465.6, ENST00000420246.6, ENST00000445888.6, ENST00000455263.6, ENST00000610292.4, ENST00000610538.4, ENST00000610623.4, ENST00000619485.4, ENST00000620739.4, ENST00000622645.4, ENST00000714356.1, ENST00000714357.1, ENST00000714359.1, ENST00000714408.1, ENST00000714409.1 )
TP53 p.Tyr220Cys (p.Y220C) ( 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
acute myeloid leukemia
Source Database
CIViC Evidence
Description
The Y220C mutation was used to create isogenic AML cell lines using MOLM13 and K526 lines. Y220C/- cells showed resistance to chemotherapeutic agents and failure to induce p21, indicating disruption of p53 function. ChIP assays demonstrated reduced p53 occupation across the genome for most p53 variants tested, including Y220C. RNAseq studies determined that a novel gene expression program was not induced in Y220C cells at baseline or with DNA damage induced p53 signal activation, and that the signature of gene expression was most similar to that of p53 loss, indicating that Y220C mutation does not induce a neomophic p53 function.
Variant Origin
Unknown
Variant Origin
Unknown
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/7527
Gene URL
https://civic.genome.wustl.edu/links/genes/45
Variant URL
https://civic.genome.wustl.edu/links/variants/922
Rating
4
Evidence Type
Functional
Disease
Acute Myeloid Leukemia
Evidence Direction
Does Not Support
Evidence Level
D
Clinical Significance
Neomorphic
Pubmed
31395785
Drugs