ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.843C>A (p.Asp281Glu) (rs1057519984)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000470818 SCV000545278 uncertain significance Li-Fraumeni syndrome 2016-07-16 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glutamic acid at codon 281 of the TP53 protein (p.Asp281Glu). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in an individual affected with adult-onset sarcoma (PMID: 23894400). Experimental studies have shown that this missense change disrupts the transcriptional transactivation function of the TP53 protein (PMID: 12826609, 18555592). Different missense substitutions at this codon (p.Asp281Asn, p.Asp281Tyr, p.Asp281Val) have been reported in individuals with TP53-related cancers (PMID: 17572079, 25293557, 10864200). This suggests that the aspartic acid residue may be critical for TP53 protein function, and that missense substitutions at this position may be pathogenic. In summary, this variant is a rare missense change that disrupts TP53 protein function. While it is absent from the population and reported in an affected individual, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Genomics and Pathology Services,Washington University in St.Louis RCV000499361 SCV000590904 uncertain significance Carcinoma of colon 2015-07-16 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000658764 SCV000780558 uncertain significance not provided 2018-02-28 criteria provided, single submitter clinical testing
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785325 SCV000923893 likely pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research

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