ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.530C>G (p.Pro177Arg) (rs751477326)

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 RCV000565979 SCV000665324 likely pathogenic Hereditary cancer-predisposing syndrome 2017-11-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Deficient protein function in appropriate functional assay(s),Other data supporting pathogenic classification
Invitae RCV000540639 SCV000629833 uncertain significance Li-Fraumeni syndrome 2017-01-26 criteria provided, single submitter clinical testing This sequence change replaces proline with arginine at codon 177 of the TP53 protein (p.Pro177Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine. The frequency data for this variant (rs751477326) in the population databases is unreliable, as metrics indicate poor quality at this position in the ExAC database. This variant has been reported in an individual affected with adrenocortical cancer (PMID: 20421238) and in an individual affected with breast cancer (PMID: 26787237). Experimental studies using yeast model systems have shown that this variant disrupts TP53 transactivation ability (PMID: 12826609). In summary, this variant is a rare missense change that disrupts protein function and has been observed in affected individuals. However, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000582953 SCV000692082 pathogenic not provided no assertion criteria provided clinical testing

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.