ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.668C>T (p.Pro223Leu) (rs138983188)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000223388 SCV000278747 uncertain significance Hereditary cancer-predisposing syndrome 2015-09-30 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),Insufficient or conflicting evidence,Co-occurence with a mutation in another gene that clearly explains a proband's phenotype
Invitae RCV000633401 SCV000754623 uncertain significance Li-Fraumeni syndrome 2018-01-08 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 223 of the TP53 protein (p.Pro223Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. 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. ClinVar contains an entry for this variant (Variation ID: 234214). Experimental studies have shown that this missense change is temperature-sensitive and is less effective than the wild-type protein in promoting apoptosis (PMID: 16741917, 27911860). An experimental study in yeast has shown that this variant partially impairs 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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