ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.818G>T (p.Arg273Leu) (rs28934576)

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Total submissions: 28
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000568814 SCV000665156 pathogenic Hereditary cancer-predisposing syndrome 2017-08-18 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Confirmed de novo alteration in the setting of a new disease (appropriate phenotype) in the family,Deficient protein function in appropriate functional assay(s),Well-characterized mutation at same position,Other strong data supporting pathogenic classification,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Database of Curated Mutations (DoCM) RCV000423981 SCV000509434 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000434695 SCV000509435 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444989 SCV000509436 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427314 SCV000509437 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437048 SCV000509438 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444109 SCV000509439 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426132 SCV000509440 likely pathogenic Adrenocortical carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436818 SCV000509441 likely pathogenic Multiple myeloma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418738 SCV000509442 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429444 SCV000509443 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000435767 SCV000509444 likely pathogenic Small cell lung cancer 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418536 SCV000509445 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000428692 SCV000509446 likely pathogenic Brainstem glioma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000438507 SCV000509447 likely pathogenic Neoplasm of the breast 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421259 SCV000509448 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431067 SCV000509449 likely pathogenic Adenocarcinoma of prostate 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000441792 SCV000509450 likely pathogenic Uterine Carcinosarcoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423633 SCV000509451 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000434296 SCV000509452 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442241 SCV000509453 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423490 SCV000509454 likely pathogenic Chronic lymphocytic leukemia 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433315 SCV000509455 likely pathogenic Acute myeloid leukemia 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444782 SCV000509456 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425890 SCV000509457 likely pathogenic Medulloblastoma 2016-05-31 no assertion criteria provided literature only
Genome Sciences Centre,British Columbia Cancer Agency RCV000515526 SCV000611151 likely pathogenic Metastatic pancreatic neuroendocrine tumours 2017-11-01 no assertion criteria provided research
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785524 SCV000924096 likely pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research
Invitae RCV000822080 SCV000962866 pathogenic Li-Fraumeni syndrome 2018-11-09 criteria provided, single submitter clinical testing This sequence change replaces arginine with leucine at codon 273 of the TP53 protein (p.Arg273Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is present in population databases (rs28934576, ExAC 0.002%). This variant has been observed in individuals affected with Li-Fraumeni-associated cancers (PMID: 10864200, 26014290). In one of this individuals the variant was observed to be de novo (PMID: 10864200). ClinVar contains an entry for this variant (Variation ID: 376655). Experimental studies have shown that this missense change impairs the transcriptional transactivation activity of the TP53 protein (PMID: 9407971, 12826609, 21343334). This variant disrupts the p.273 amino acid residue in TP53. Other variants that disrupt this residue have been observed in affected individuals (PMID: 9242456, 21484931, 17540308, 1565144, 20693561, 21552135), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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