ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.374C>G (p.Thr125Arg) (rs786201057)

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Total submissions: 22
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000492090 SCV000581128 likely pathogenic Hereditary cancer-predisposing syndrome 2014-11-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Deficient protein function in appropriate functional assay(s),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Rarity in general population databases (dbsnp, esp, 1000 genomes),Other data supporting pathogenic classification,Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Database of Curated Mutations (DoCM) RCV000428977 SCV000509821 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000440628 SCV000509822 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423368 SCV000509823 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429727 SCV000509824 likely pathogenic Acute myeloid leukemia 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000440402 SCV000509825 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000424026 SCV000509826 likely pathogenic Squamous cell carcinoma of the skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000434737 SCV000509827 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442755 SCV000509828 likely pathogenic Brainstem glioma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423812 SCV000509829 likely pathogenic Renal cell carcinoma, papillary, 1 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000432131 SCV000509830 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442833 SCV000509831 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000424710 SCV000509832 likely pathogenic Small cell lung cancer 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436286 SCV000509833 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442028 SCV000509834 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425385 SCV000509835 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436088 SCV000509836 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000419630 SCV000509837 likely pathogenic Neoplasm of the breast 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430321 SCV000509838 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436638 SCV000509839 likely pathogenic Adrenocortical carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000419385 SCV000509840 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Invitae RCV000524926 SCV000629809 uncertain significance Li-Fraumeni syndrome 2018-12-12 criteria provided, single submitter clinical testing This sequence change replaces threonine with arginine at codon 125 of the TP53 protein (p.Thr125Arg). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with Li-Fraumeni syndrome cancers (PMID: 18511570, 20127978, 20522432), and an individual with hypodiploid acute lymphoblastic leukemia (PMID: 26580448). ClinVar contains an entry for this variant (Variation ID: 376667). Experimental studies have shown that this variant disrupts the function of the TP53 protein (PMID: 12826609, 16508005, 27533082, 17401428). In summary, this variant is a rare missense change that is absent from the population, reported in affected individuals, and has been shown to disrupt protein function in vitro. However, 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.

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