ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.718A>G (p.Ser240Gly)

dbSNP: rs1567549584
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000989712 SCV001140254 likely pathogenic Squamous cell carcinoma of the head and neck 2019-05-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000709404 SCV001228935 likely pathogenic Li-Fraumeni syndrome 2022-02-18 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects TP53 function (PMID: 12826609, 29979965, 30224644). Advanced modeling of experimental studies (such as gene expression, population dynamics, functional pathways, and cell-cycle effects in cell culture) performed at Invitae indicates that this missense variant is expected to disrupt TP53 protein function. ClinVar contains an entry for this variant (Variation ID: 584921). This missense change has been observed in individuals with Li-Fraumeni syndrome (PMID: 27391063, 27501770). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 240 of the TP53 protein (p.Ser240Gly).
Genome-Nilou Lab RCV002289987 SCV002582365 likely pathogenic Hereditary cancer-predisposing syndrome 2022-06-18 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002289986 SCV002583026 likely pathogenic Li-Fraumeni syndrome 1 2022-06-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV002289987 SCV002668525 pathogenic Hereditary cancer-predisposing syndrome 2022-03-28 criteria provided, single submitter clinical testing The p.S240G variant (also known as c.718A>G), located in coding exon 6 of the TP53 gene, results from an A to G substitution at nucleotide position 718. The serine at codon 240 is replaced by glycine, an amino acid with similar properties. This variant is in the DNA binding domain of the TP53 protein and is reported to have non-functional transactivation in yeast based assays (Kato S et al. Proc. Natl. Acad. Sci. USA. 2003 Jul;100:8424-9). Studies conducted in human cell lines indicate this alteration is deficient at growth suppression and has a dominant negative effect (Kotler E et al. Mol.Cell. 2018 Jul;71:178-190.e8; Giacomelli AO et al. Nat. Genet. 2018 Oct;50:1381-1387). This mutation has also been reported in a proband with Li-Fraumeni syndrome diagnosed with adrenocortical carcinoma at 1 year of age (Villani A et al. Lancet Oncol 2016 Sep;17(9):1295-305). This amino acid position is highly 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.

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.