ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.835G>A (p.Gly279Arg) (rs1555525248)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000566142 SCV000672406 uncertain significance Hereditary cancer-predisposing syndrome 2017-12-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000547189 SCV000629876 uncertain significance Li-Fraumeni syndrome 2017-07-27 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 279 of the TP53 protein (p.Gly279Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in an individual affected with sarcoma (PMID: 23894400). An experimental study has shown that this missense change disrupts TP53 transactivational activity in yeast (PMID: 12826609). However, it has been shown to  cause cell death comparable to WT when expressed in yeast and mammalian cells and to confer a moderate protection to radiation in mammalian cell cultures (PMID: 11423991, 12909720, 16508005). The clinical relevance of these findings is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.