ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.809T>G (p.Phe270Cys)

dbSNP: rs1057519986
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 14
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001805037 SCV002052524 likely pathogenic Hereditary cancer-predisposing syndrome 2023-02-21 criteria provided, single submitter clinical testing This missense variant replaces phenylalanine with cysteine at codon 270 of the TP53 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have shown that the mutant is defective in transcriptional transactivation of TP53 target genes, displays loss of function and dominant negative activity in human cell growth suppression assays, and is non-functional in human cell proliferation assays (PMID: 12826609, 29979965, 30224644). This variant has been observed germline in two individuals suspected of having Li-Fraumeni syndrome (PMID: 32817165). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic.
GeneDx RCV002508212 SCV002817846 likely pathogenic not provided 2022-12-28 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect: non-functional transactivation, loss of growth suppression ability, and dominant negative effect (Kato et al., 2003; Dearth et al., 2007; Giacomelli et al., 2018; Kotler et al., 2018); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported in the literature in families with Li-Fraumeni syndrome (Gao et al., 2020); This variant is associated with the following publications: (PMID: 15510160, 26619011, 32817165, 32358561, 29979965, 28160562, 30808373, 27662657, 16861262, 15308588, 30224644, 12826609)
Invitae RCV002524696 SCV003317121 uncertain significance Li-Fraumeni syndrome 2022-03-26 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 270 of the TP53 protein (p.Phe270Cys). 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: 32817165). ClinVar contains an entry for this variant (Variation ID: 376597). 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. 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.
Baylor Genetics RCV003470375 SCV004206230 likely pathogenic Adrenocortical carcinoma, hereditary 2023-09-22 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV004022213 SCV004932392 likely pathogenic Li-Fraumeni syndrome 1 2024-02-20 criteria provided, single submitter clinical testing This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 7651740, 10713666, 29979965]. This variant is expected to disrupt protein structure [Myriad internal data].
Database of Curated Mutations (DoCM) RCV000441020 SCV000508116 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000424190 SCV000508117 likely pathogenic Gastric adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000434574 SCV000508118 likely pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000440467 SCV000508119 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000422786 SCV000508120 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433925 SCV000508121 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443933 SCV000508122 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000422121 SCV000508123 likely pathogenic Ovarian serous cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000432351 SCV000508124 likely pathogenic Squamous cell carcinoma of the skin 2016-05-31 no assertion criteria provided literature only

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.