ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.800G>C (p.Arg267Pro) (rs587780075)

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 RCV000492273 SCV000581097 likely pathogenic Hereditary cancer-predisposing syndrome 2016-04-04 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Other data supporting pathogenic classification
Invitae RCV000691629 SCV000819415 uncertain significance Li-Fraumeni syndrome 2018-03-22 criteria provided, single submitter clinical testing This sequence change replaces arginine with proline at codon 267 of the TP53 protein (p.Arg267Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported as a germline variant in individuals affected with TP53-related disease. ClinVar contains an entry for this variant (Variation ID: 428867). An experimental study in yeast has shown that this variant impairs the transcriptional transactivation activity of the TP53 protein (PMID: 12826609). In addition, experimental studies using a lung cancer cell line that carries this variant demonstrates elevated Axl expression and enhanced cell growth, while p21 promoter activity appears unaffected (PMID: 23264849, 22989750). 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.