Annotation Detail

Information
Associated Genes
PTEN
Associated Variants
PTEN p.Arg173Cys (p.R173C) ( ENST00000472832.3, ENST00000371953.8, ENST00000688308.1, ENST00000700021.1, ENST00000700029.2, ENST00000713839.1 )
PTEN p.Arg173Cys (p.R173C) ( ENST00000371953.8, ENST00000472832.3, ENST00000688308.1, ENST00000700021.1, ENST00000700029.2, ENST00000713839.1 )
Associated Disease
cancer
Source Database
CIViC Evidence
Description
Han et al functionally tested the R173C mutation in PTEN using an expression vector construct, assessing phosphatase activity of the mutant construct with two phosphoinositide substrates ("with[ PtdIns(3,4,5)P3] or without[ Ins(1,3,4,5)P4] a diacylglycerol chain"). R173C resides in the NH2-terminal phosphatase domain of PTEN. R173C was one of four mutations (out of 42 tested) that displayed no significant phosphatase activity against either substrate, indicating, by this assay, that the mutation negatively impacts the function of PTEN. However this mutation did not affect the ability of PTEN to bind lipid membranes in-vivo. This data justifies PS3 level evidence for pathogenicity according to ACMG guidelines.
Variant Origin
N/A
Variant Origin
N/A
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1930
Gene URL
https://civic.genome.wustl.edu/links/genes/41
Variant URL
https://civic.genome.wustl.edu/links/variants/838
Rating
3
Evidence Type
Predisposing
Disease
Cancer
Evidence Direction
Supports
Evidence Level
D
Clinical Significance
Uncertain Significance
Pubmed
10866302
Drugs