ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.470T>A (p.Val157Asp)

dbSNP: rs1131691023
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 RCV000561132 SCV000667207 pathogenic Hereditary cancer-predisposing syndrome 2024-07-03 criteria provided, single submitter clinical testing The p.V157D pathogenic mutation (also known as c.470T>A), located in coding exon 4 of the TP53 gene, results from a T to A substitution at nucleotide position 470. The valine at codon 157 is replaced by aspartic acid, an amino acid with highly dissimilar properties. This variant has also reported in a tumor and the germline of a patient with lung cancer at age 22, and a family history of multiple early-onset cancers; functional analysis of p.V157D showed impaired p51 transactivation ability (Wang Z et al. Cancer Lett. 2014 Jan;342:36-42). Studies conducted in human cell lines indicate this alteration is deficient at growth suppression (Kotler E et al. Mol. Cell 2018 Jul;71:178-190.e8; Giacomelli AO et al. Nat. Genet. 2018 Oct;50:1381-1387). Furthermore, alterations at the same location (p.V157A, p.V157F) have been reported in families meeting Li-Fraumeni-like syndrome criteria are anticipated to result in a significant decrease in structural stability of the DNA-binding domain (Cho Y et al. Science. 1994 Jul; 265(5170):346-55; Kitayner et al. Nat. Struct. Mol. Biol. 2010 Apr;17(4):423-9; Calhoun S et al. Biochemistry. 2011 Jun;50:5345-53). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp RCV000807881 SCV000947957 uncertain significance Li-Fraumeni syndrome 2022-10-25 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 157 of the TP53 protein (p.Val157Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of Li-Fraumeni syndrome (PMID: 23981578, 32994724). ClinVar contains an entry for this variant (Variation ID: 482231). 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, 23981578, 29979965, 30224644). 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.
Myriad Genetics, Inc. RCV004024481 SCV004932755 likely pathogenic Li-Fraumeni syndrome 1 2024-02-14 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].

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.