ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.1079G>A (p.Gly360Glu) (rs35993958)

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 RCV000213880 SCV000273804 uncertain significance Hereditary cancer-predisposing syndrome 2016-01-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),Insufficient or conflicting evidence,In silico models in agreement (benign)
Invitae RCV000541338 SCV000629770 uncertain significance Li-Fraumeni syndrome 2017-10-23 criteria provided, single submitter clinical testing This sequence change replaces glycine with glutamic acid at codon 360 of the TP53 protein (p.Gly360Glu). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a TP53-related disease. ClinVar contains an entry for this variant (Variation ID: 230306). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The glutamic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. However, yeast-based functional assays have shown that this missense change results in partial loss of TP53 transactivation activity (PMID: 12826609). 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.