ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.140C>G (p.Pro47Arg) (rs1597375038)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001011436 SCV001171757 likely benign Hereditary cancer-predisposing syndrome 2019-08-07 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other data supporting benign classification
Color Health, Inc RCV001011436 SCV001340840 uncertain significance Hereditary cancer-predisposing syndrome 2020-10-06 criteria provided, single submitter clinical testing This missense variant replaces proline with arginine at codon 47 of the TP53 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Functional studies have that this variant protein is functional in yeast transactivation activity assay and in human cells (PMID: 12826609, 30224644). To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Invitae RCV001242916 SCV001416037 uncertain significance Li-Fraumeni syndrome 2019-09-30 criteria provided, single submitter clinical testing This sequence change replaces proline with arginine at codon 47 of the TP53 protein (p.Pro47Arg). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and arginine. 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 conditions. This variant has been reported not to substantially affect TP53 protein function (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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