ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.833C>G (p.Pro278Arg) (rs876659802)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 17
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000572417 SCV000672393 uncertain significance Hereditary cancer-predisposing syndrome 2016-06-20 criteria provided, single submitter clinical testing The p.P278R variant (also known as c.833C>G), located in coding exon 7 of the TP53 gene, results from a C to G substitution at nucleotide position 833. The proline at codon 278 is replaced by arginine, an amino acid with dissimilar properties. This alteration was shown to have a loss of transactivation capacity in yeast-based functional studies (Kato S et al. Proc Natl Acad Sci USA. 2003 Jul 8;100(14):8424-9). This alteration has been identified in numerous different tumor types across multiple studies (Hao XD et al. Oncol. Rep. 2013 Jan; 29(1):226-3.; Hassan NM et al. Cancer Lett. 2008 Oct; 270(1):108-19; Houben R et al, PLoS ONE 2011 Jul; 6(7):e22096; Marchetti P et al. Ann. Oncol. 2003 May; 14(5):704-8). <span style="font-family:arial,sans-serif">Other alterations at this same amino acid position (p.P278A, p.P278S, p.P278T) <span style="font-family:arial,sans-serif"> have previously been reported in the germline of individuals diagnosed with Li-Fraumeni syndrome (Bougeard G et al. J. Med. Genet<span style="font-family:arial,sans-serif">. 2001 Apr; 38(4):253-7; G&uuml;ran S et al. Cancer Genet. Cytogenet<span style="font-family:arial,sans-serif">. 2005 Jul; 160(2):164-8; Speiser P et al. Br. J. Cancer <span style="font-family:arial,sans-serif">1996 Jul; 74(2):269-73). This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.0004% (greater than 250000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis.Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000797363 SCV000936917 uncertain significance Li-Fraumeni syndrome 2018-11-05 criteria provided, single submitter clinical testing This sequence change replaces proline with arginine at codon 278 of the TP53 protein (p.Pro278Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in the germline of individuals with TP53-related disease.  ClinVar contains an entry for this variant (Variation ID: 376644). Experimental studies have shown that this variant impairs the transcriptional transactivation activity of the TP53 protein (PMID: 12826609, 20195489, 26619011) 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.
Database of Curated Mutations (DoCM) RCV000424036 SCV000509073 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431305 SCV000509074 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000441126 SCV000509075 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423863 SCV000509076 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431945 SCV000509077 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443990 SCV000509078 likely pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000420956 SCV000509079 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431661 SCV000509080 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444083 SCV000509081 likely pathogenic Multiple myeloma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425930 SCV000509082 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000432244 SCV000509083 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443337 SCV000509084 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426582 SCV000509085 likely pathogenic Squamous cell carcinoma of the skin 2016-05-31 no assertion criteria provided literature only
Gharavi Laboratory,Columbia University RCV000681956 SCV000809448 likely pathogenic not provided 2018-09-16 no assertion criteria provided research
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785498 SCV000924070 likely pathogenic Neoplasm of ovary 2018-12-01 no assertion criteria provided research

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.