ClinVar Miner

Submissions for variant NM_001126112.2(TP53):c.343C>A (p.His115Asn) (rs1555526532)

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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 RCV000576064 SCV000664407 uncertain significance Hereditary cancer-predisposing syndrome 2016-06-02 criteria provided, single submitter clinical testing Insufficient evidence
Invitae RCV000821053 SCV000961794 uncertain significance Li-Fraumeni syndrome 2018-09-29 criteria provided, single submitter clinical testing This sequence change replaces histidine with asparagine at codon 115 of the TP53 protein (p.His115Asn). The histidine residue is weakly conserved and there is a small physicochemical difference between histidine and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TP53-related disease. ClinVar contains an entry for this variant (Variation ID: 480741). An experimental study in yeast has shown that this variant does not impair the transcriptional transactivation activity of the TP53 protein (PMID: 12826609). Additional studies have reported conflicting results that while this variant is effective in binding to DNA and inducing cell cycle arrest in G1, it results in a protein with impaired apoptosis response upon DNA damage stress (PMID: 20113312, 19462533). 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.

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