ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.408A>C (p.Gln136His) (rs758781593)

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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 RCV000165874 SCV000216624 uncertain significance Hereditary cancer-predisposing syndrome 2014-09-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Deficient protein function in appropriate functional assay(s),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Rarity in general population databases (dbsnp, esp, 1000 genomes)
Invitae RCV000229644 SCV000285194 uncertain significance Li-Fraumeni syndrome 2016-03-05 criteria provided, single submitter clinical testing This sequence change replaces glutamine with histidine at codon 136 of the TP53 protein (p.Gln136His). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with prostate cancer (PMID: 16941491). ClinVar contains an entry for this variant (Variation ID: 186301). Experimental studies in yeast have shown that this missense change disrupts TP53 transactivation activity (PMID: 12826609). In summary, this variant has been observed in an individual with prostate cancer and has been shown to disrupt TP53 function. However, in the absence of additional genetic and/or functional data, it has been classified as a Variant of Uncertain Significance.

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