ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.476C>T (p.Ala159Val) (rs1555526131)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000527533 SCV000629826 uncertain significance Li-Fraumeni syndrome 2017-08-28 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 159 of the TP53 protein (p.Ala159Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature as a germline variant in individuals with TP53-related disease. Experimental studies have shown that this missense change reduces the transcriptional transactivation activity of the TP53 protein in yeast-based assays (PMID: 12826609), acting as a temperature dependent mutation that is inactive at physiological temperature (PMID: 17724467, 22862161). 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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