ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.100C>A (p.Pro34Thr) (rs786201968)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164526 SCV000215180 likely benign Hereditary cancer-predisposing syndrome 2018-02-02 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other data supporting benign classification
Invitae RCV000471959 SCV000545341 uncertain significance Li-Fraumeni syndrome 2020-08-11 criteria provided, single submitter clinical testing This sequence change replaces proline with threonine at codon 34 of the TP53 protein (p.Pro34Thr). The proline residue is weakly conserved and there is a small physicochemical difference between proline and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TP53-related disease. ClinVar contains an entry for this variant (Variation ID: 185157). An experimental study in yeast has shown that this variant does not impair the transcriptional transactivation activity of the TP53 protein (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.
Color Health, Inc RCV000164526 SCV000908805 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-13 criteria provided, single submitter clinical testing
GeneDx RCV001582646 SCV001811945 uncertain significance not provided 2019-11-20 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Published functional studies demonstrate no damaging effect: transactivation and growth suppression activity comparable to wild type (Kato 2003, Giacomelli 2018); This variant is associated with the following publications: (PMID: 30886117, 30224644, 12826609)

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.