ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.653T>G (p.Val218Gly) (rs1555525743)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000633350 SCV000754572 uncertain significance Li-Fraumeni syndrome 2018-01-03 criteria provided, single submitter clinical testing This sequence change replaces valine with glycine at codon 218 of the TP53 protein (p.Val218Gly). The valine residue is highly conserved and there is a moderate physicochemical difference between valine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TP53-related disease. A different missense substitution at this codon (p.Val218Met) has been determined to be pathogenic (Invitae). This suggests that the valine residue may be critical for TP53 protein function. However, an experimental study in yeast has shown that the p.Val218Gly missense change does not impair the transcriptional transactivation activity of the TP53 protein (PMID: 12826609). 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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