ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.537T>A (p.His179Gln) (rs876660821)

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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 RCV000567952 SCV000664423 likely pathogenic Hereditary cancer-predisposing syndrome 2016-09-02 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Deficient protein function in appropriate functional assay(s),Other data supporting pathogenic classification,Well-characterized mutation at same position
Invitae RCV000464573 SCV000545303 pathogenic Li-Fraumeni syndrome 2018-04-12 criteria provided, single submitter clinical testing This sequence change replaces histidine with glutamine at codon 179 of the TP53 protein (p.His179Gln). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been reported de novo in an individual with Li-Fraumeni syndrome (PMID: 19556618), and in an individual affected with follicular lymphoma (PMID: 18628487). ClinVar contains an entry for this variant (Variation ID: 406578). Experimental studies have shown that this missense change results in defective TP53 transactivation activity and severely attenuated cell-cycle checkpoint function (PMID: 12826609, 17311302, 16209708, 22540896). For these reasons, this variant has been classified as Pathogenic.

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