Description
This variant is denoted TP53 c.701A>G at the cDNA level and p.Tyr234Cys (Y234C) at the protein level, and results in the change of a Tyrosine to a Cysteine (TAC>TGC) in exon 7. This TP53 Tyr234Cys has previously been identified in over 100 tumors as a somatic mutation, most frequently in tumors of the lung, ovaries, brain, breast, and bladder (Petitjean 2007). In addition, this mutation has been observed as a germline mutation in at least one patient with Li Fraumeni syndrome (Pepper 2003). Functional studies have shown loss of transcriptional activation, loss of growth arrest, and loss of induction of apoptosis for this mutation as compared to wild type (Smith 1999, Monti 2007, Monti 2011). Smith et al. (1999) identified that this mutation failed to suppress oncogenic transformation and instead acts as a gain of function mutation, enhancing oncogenic transformation. This variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Variant Server, suggesting it is not a common benign variant in these populations. This variant is a non-conservative amino acid, altering a position that is well conserved throughout evolution, and is located in the DNA domain which interacts with HIPK1, ZNF385A, FOXO42, and AXIN1 (UniProt). Multiple in silico algorithms predict that this variant may be damaging to protein structure and function. We therefore consider this mutation to be pathogenic. This variant has been seen apparently mosaic. The variant is found in ENDOM-HEREDIC panel(s).
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
