ClinVar Miner

Submissions for variant NM_001126112.2(TP53):c.463A>G (p.Thr155Ala) (rs772683278)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000534841 SCV000629821 uncertain significance Li-Fraumeni syndrome 2017-05-10 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 155 of the TP53 protein (p.Thr155Ala). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs772683278, ExAC 0.006%) but has not been reported in the literature in the germline of individuals with a TP53-related disease. An experimental study has reported that this variant was able to transactivate the p21 gene promoter in vitro and it was degraded by HPV16 E6 oncoprotein to a similar extent as the wild-type TP53 protein (PMID: 22046250). In addition, a separate study in yeast testing TP53 transactivation activity using 8 different promoters classifies this missense change as functional (PMID: 12826609). In summary, this variant is a rare missense change that has been shown not to significantly affect protein function in vitro. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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