ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.766A>G (p.Thr256Ala) (rs587781433)

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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 RCV000129326 SCV000184089 likely pathogenic Hereditary cancer-predisposing syndrome 2013-11-15 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Well-characterized mutation at same position,Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Other data supporting pathogenic classification
Invitae RCV000688741 SCV000816364 uncertain significance Li-Fraumeni syndrome 2018-06-26 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 256 of the TP53 protein (p.Thr256Ala). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with Li-Fraumeni syndrome (PMID: 20127978). ClinVar contains an entry for this variant (Variation ID: 141011). An experimental study in yeast has shown that this variant partially impairs the transcriptional transactivation activity of the TP53 protein (PMID: 12826609). However, another experimental study has shown that this variant does not affect the TP53 protein function (PMID: 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.
Pathway Genomics RCV000172827 SCV000223793 uncertain significance Li-Fraumeni syndrome 1 2014-10-30 criteria provided, single submitter clinical testing

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