ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.752T>A (p.Ile251Asn)

dbSNP: rs730882027
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
Labcorp Genetics (formerly Invitae), Labcorp RCV000633360 SCV000754582 uncertain significance Li-Fraumeni syndrome 2023-06-17 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with clinical features of TP53-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 528254). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is expected to disrupt TP53 function. Experimental studies have shown that this missense change affects TP53 function (PMID: 12826609, 29979965, 30224644). This variant disrupts the p.Ile251 amino acid residue in TP53. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12826609, 21305319, 27501770, 29979965, 30224644). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. This sequence change replaces isoleucine, which is neutral and non-polar, with asparagine, which is neutral and polar, at codon 251 of the TP53 protein (p.Ile251Asn). This variant is not present in population databases (gnomAD no frequency).
All of Us Research Program, National Institutes of Health RCV000633360 SCV004827010 uncertain significance Li-Fraumeni syndrome 2023-04-27 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV004025427 SCV004932388 likely pathogenic Li-Fraumeni syndrome 1 2024-02-16 criteria provided, single submitter clinical testing This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 29979965]. This variant is expected to disrupt protein structure [Myriad internal data].
Cancer Genetics Lab, University of Education RCV003228966 SCV003926524 pathogenic Acute myeloid leukemia 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.