ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.733G>C (p.Gly245Arg) (rs28934575)

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Total submissions: 17
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000633351 SCV000754573 uncertain significance Li-Fraumeni syndrome 2017-09-11 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 245 of the TP53 protein (p.Gly245Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with childhood acute lymphoblastic leukemia, although it was not determined if this variant was a germline or somatic alteration (PMID: 21747090). ClinVar contains an entry for this variant (Variation ID: 376604). Experimental studies have shown that this missense change impairs the transactivation activity of the p53 protein in vitro (PMID: 12826609). Different missense substitutions at this codon (p.Gly245Val, p.Gly245Ser, and p.Gly245Asp) have been determined to be pathogenic (PMID: 21343334, 11920788, 2259385, 20128691, 1565143). This suggests that the glycine residue is critical for TP53 protein function and that other missense substitutions at this position may also be pathogenic. In summary, this is a missense change that disrupts TP53 protein function and is absent from the population. In the absence of additional clinical data the evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance
Database of Curated Mutations (DoCM) RCV000432081 SCV000508247 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444128 SCV000508248 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000424643 SCV000508249 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431462 SCV000508250 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444043 SCV000508251 likely pathogenic Brainstem glioma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425790 SCV000508252 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436041 SCV000508253 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418277 SCV000508254 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426804 SCV000508255 likely pathogenic Neoplasm of the breast 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437043 SCV000508256 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000419444 SCV000508257 likely pathogenic Adenocarcinoma of prostate 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429713 SCV000508258 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000441708 SCV000508259 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000420527 SCV000508260 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430767 SCV000508261 likely pathogenic Uterine Carcinosarcoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439119 SCV000508262 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only

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