ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.826G>C (p.Ala276Pro) (rs1131691029)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000492584 SCV000581144 pathogenic Hereditary cancer-predisposing syndrome 2017-03-02 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other data supporting pathogenic classification,Deficient protein function in appropriate functional assay(s),Structural Evidence,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Confirmed de novo alteration in the setting of a new disease (appropriate phenotype) in the family
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785453 SCV000924025 likely pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research
Invitae RCV000705570 SCV000834572 uncertain significance Li-Fraumeni syndrome 2018-03-30 criteria provided, single submitter clinical testing This sequence change replaces alanine with proline at codon 276 of the TP53 protein (p.Ala276Pro). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with a TP53-related disease. ClinVar contains an entry for this variant (Variation ID: 428893). Experimental in vitro studies have shown that this missense change results in almost null TP53 DNA-binding and transactivation activity, and that it may act in a dominant-negative manner in decreasing TP53 wild-type activity (PMID: 12826609, 16861262). 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.