ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.1118A>G (p.Lys373Arg) (rs1567540504)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000771476 SCV000903934 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-30 criteria provided, single submitter clinical testing
Invitae RCV000700219 SCV000828967 uncertain significance Li-Fraumeni syndrome 2018-11-13 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 373 of the TP53 protein (p.Lys373Arg). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been published in the literature, but has not been observed in individuals with TP53-related disease. ClinVar contains an entry for this variant (Variation ID: 577458). Experimental studies have shown that this missense change has no effect on the transactivation ability of TP53 in vitro but causes a reduction in the activation of a reporter gene and reduces apoptosis (PMID: 12716906, 12826609, 22178617, 27911860, 17977830). Additionally, this residue has been shown to be a target for acetylation and methylation which modulates the protein's function (PMID: 14695212, 29774081). 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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