ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.700T>C (p.Tyr234His) (rs864622237)

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Total submissions: 17
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000492782 SCV000581136 pathogenic Hereditary cancer-predisposing syndrome 2016-02-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Confirmed de novo alteration in the setting of a new disease (appropriate phenotype) in the family,Deficient protein function in appropriate functional assay(s),Other data supporting pathogenic classification,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Database of Curated Mutations (DoCM) RCV000427499 SCV000510313 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436907 SCV000510314 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000419222 SCV000510315 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426894 SCV000510316 likely pathogenic Adrenocortical carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437128 SCV000510317 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418604 SCV000510318 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000428839 SCV000510319 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439967 SCV000510320 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418790 SCV000510321 likely pathogenic Small cell lung cancer 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000428164 SCV000510322 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000438411 SCV000510323 likely pathogenic Neoplasm of the breast 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421640 SCV000510324 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431867 SCV000510325 likely pathogenic Adenocarcinoma of prostate 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000441352 SCV000510326 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785304 SCV000923872 likely pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research
Invitae RCV000530551 SCV000629855 uncertain significance Li-Fraumeni syndrome 2017-06-13 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with histidine at codon 234 of the TP53 protein (p.Tyr234His). The tyrosine residue is highly conserved and there is a moderate physicochemical difference between tyrosine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with breast cancer and leiomyosarcoma (PMID: 23894400). ClinVar contains an entry for this variant (Variation ID: 376691). Experimental studies have shown that this missense change affects transactivation activity of the TP53 protein, is unable to induce p53-responsive MDM2, and has transforming activity as well as mild gain-of-function activity in vitro (PMID: 10871862, 10229196, 11429705, 8080050, 11896595, 22710932, 9525742, 12826609). In summary, this variant has been shown to affect TP53 function. However, segregation studies have not been reported and the available clinical genetic evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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