ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.747G>C (p.Arg249Ser) (rs28934571)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000465003 SCV000545346 uncertain significance Li-Fraumeni syndrome 2016-07-16 criteria provided, single submitter clinical testing This sequence change replaces arginine with serine at codon 249 of the TP53 protein (p.Arg249Ser). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and serine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a TP53-related disease. However, this variant has been identified as a hot spot in hepatocellular carcinoma and is the 7th most frequent single codon p53 mutation found in human cancer biopsies (PMID: 1849234, 19756158, 20538734, 15095302, 17311302). ClinVar contains an entry for this variant (Variation ID: 12352). Experimental studies have shown that this missense change affects TP53 protein structure and disrupts protein function (PMID: 15703170, 15982667, 9405613, 12826609, 20538734, 15060172, 18477611). In summary, this variant is a rare missense change that disrupts protein function. While it is absent from the population and reported in many cancer cell biopsies, the available 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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