ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.770T>C (p.Leu257Pro) (rs28934577)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000540536 SCV000629867 uncertain significance Li-Fraumeni syndrome 2018-04-09 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 257 of the TP53 protein (p.Leu257Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). While this variant has been published in the literature (PMID: 8633021, 11896595, 16861262, 9572492, 15825182, 11429705, 12826609), it has not been reported in an individual with a TP53-related disease. ClinVar contains an entry for this variant (Variation ID: 458562). Experimental studies have shown that this missense change disrupts transcriptional transactivaction of the TP53 protein function and acts in a dominant negative manner in yeast-based assays (PMID: 8633021, 11896595, 16861262, 9572492, 15825182, 11429705, 12826609). In summary, this variant has shown to affect TP53 protein function. In the absence of additional data, 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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