ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.40C>G (p.Leu14Val)

dbSNP: rs1567558112
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 RCV000699996 SCV000828730 uncertain significance Li-Fraumeni syndrome 2018-05-16 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals with TP53-related disease. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. An experimental study in yeast has shown that this variant does not impair the transcriptional transactivation activity of the TP53 protein (PMID: 12826609). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with valine at codon 14 of the TP53 protein (p.Leu14Val). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and valine.
Color Diagnostics, LLC DBA Color Health RCV001187937 SCV001354879 uncertain significance Hereditary cancer-predisposing syndrome 2019-12-23 criteria provided, single submitter clinical testing This missense variant replaces leucine with valine at codon 14 of the TP53 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Functional studies showed that this variant is functional in IARC yeast transactivation assays (IARC database and PMID: 12826609), and it had no dominant negative and no loss of function effects in human cell growth suppression assays (PMID: 30224644) . This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Genome-Nilou Lab RCV001187937 SCV002582176 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-18 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002289976 SCV002582739 uncertain significance Li-Fraumeni syndrome 1 2022-06-18 criteria provided, single submitter 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.