ClinVar Miner

Submissions for variant NM_001126112.2(TP53):c.826G>C (p.Ala276Pro) (rs1131691029)

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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 RCV000492584 SCV000581144 pathogenic Hereditary cancer-predisposing syndrome 2017-03-02 criteria provided, single submitter clinical testing Other data supporting pathogenic classification;Deficient protein function in appropriate functional assay(s);Structural Evidence;In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Confirmed de novo alteration in the setting of a new disease (appropriate phenotype) in the family
Invitae RCV000705570 SCV000834572 uncertain significance Li-Fraumeni syndrome 2019-08-14 criteria provided, single submitter clinical testing This sequence change replaces alanine with proline at codon 276 of the TP53 protein (p.Ala276Pro). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with a TP53-related disease. ClinVar contains an entry for this variant (Variation ID: 428893). Experimental in vitro studies have shown that this missense change results in almost null TP53 DNA-binding and transactivation activity, and that it may act in a dominant-negative manner in decreasing TP53 wild-type activity (PMID: 12826609, 16861262). 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.
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785453 SCV000924025 likely pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research

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