ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.581T>G (p.Leu194Arg) (rs1057519998)

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000561306 SCV000676299 uncertain significance Hereditary cancer-predisposing syndrome 2016-02-09 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient or conflicting evidence,Co-occurence with mutation in same gene (phase unknown),Other data supporting pathogenic classification
Database of Curated Mutations (DoCM) RCV000424933 SCV000508836 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437791 SCV000508837 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000420755 SCV000508838 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431014 SCV000508839 likely pathogenic Neoplasm of the breast 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436915 SCV000508840 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000419180 SCV000508841 likely pathogenic Uterine cervical neoplasms 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430366 SCV000508842 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000440633 SCV000508843 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000422070 SCV000508844 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000428827 SCV000508845 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439886 SCV000508846 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785551 SCV000924123 likely pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research
Invitae RCV000535418 SCV000629844 uncertain significance Li-Fraumeni syndrome 2018-01-10 criteria provided, single submitter clinical testing This sequence change replaces leucine with arginine at codon 194 of the TP53 protein (p.Leu194Arg). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TP53-related disease. ClinVar contains an entry for this variant (Variation ID: 376633). Experimental studies in yeast and human non-small cell lung carcinoma cell lines demonstrate that this missense change has defective transactivation activity, does not interact with MDM2, fails to suppress cell growth, and has reduced induction of TP53 downstream target genes following fludarabine administration (PMID: 12826609, 20407015, 12509279, 19850740). 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.

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