ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.464C>A (p.Thr155Asn) (rs786202752)

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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 RCV000492645 SCV000581130 likely pathogenic Hereditary cancer-predisposing syndrome 2015-01-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Deficient protein function in appropriate functional assay(s),Rarity in general population databases (dbsnp, esp, 1000 genomes),Other data supporting pathogenic classification,Structural Evidence
Invitae RCV000473602 SCV000545261 uncertain significance Li-Fraumeni syndrome 2016-04-22 criteria provided, single submitter clinical testing This sequence change replaces threonine with asparagine at codon 155 of the TP53 protein (p.Thr155Asn). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual with glioblastoma multiforme at age 32 and family history of mother with astrocytoma at age 38 and maternal grandfather with liver and pancreatic cancer at age 72 (PMID: 8308926, 17606709). This variant is located in the TP53 DNA binding domain, which is required for proper protein function (PMID: 26205489). Experimental studies have shown that this missense change severely affects the functional activity of p53 protein by abolishing its transactivational activity. This variant is classified as a severe deficiency allele with a possible dominant-negative inhibitory effect (PMID: 12826609, 21343334, 17606709). In summary, this variant is a rare missense change that has been reported in an affected individual and is absent from the general population. Although there is experimental evidence suggesting that this change severely affects protein function, in the absence of segregation evidence it has been classified as a Variant of Uncertain Significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000506226 SCV000602271 uncertain significance not specified 2017-01-19 criteria provided, single submitter clinical testing

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