ClinVar Miner

Submissions for variant NM_001126112.2(TP53):c.800G>C (p.Arg267Pro) (rs587780075)

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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 RCV000492273 SCV000581097 likely pathogenic Hereditary cancer-predisposing syndrome 2019-07-15 criteria provided, single submitter clinical testing Rarity in general population databases (dbsnp, esp, 1000 genomes);In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Structural Evidence;Deficient protein function in appropriate functional assay(s)
Invitae RCV000691629 SCV000819415 uncertain significance Li-Fraumeni syndrome 2018-03-22 criteria provided, single submitter clinical testing This sequence change replaces arginine with proline at codon 267 of the TP53 protein (p.Arg267Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported as a germline variant in individuals affected with TP53-related disease. ClinVar contains an entry for this variant (Variation ID: 428867). An experimental study in yeast has shown that this variant impairs the transcriptional transactivation activity of the TP53 protein (PMID: 12826609). In addition, experimental studies using a lung cancer cell line that carries this variant demonstrates elevated Axl expression and enhanced cell growth, while p21 promoter activity appears unaffected (PMID: 23264849, 22989750). 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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