ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.1104C>G (p.His368Gln) (rs1289241865)

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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 RCV000575539 SCV000672402 uncertain significance Hereditary cancer-predisposing syndrome 2016-10-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000798387 SCV000938003 uncertain significance Li-Fraumeni syndrome 2018-07-17 criteria provided, single submitter clinical testing This sequence change replaces histidine with glutamine at codon 368 of the TP53 protein (p.His368Gln). The histidine residue is weakly conserved and there is a small physicochemical difference between histidine and glutamine. 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: 485038). An experimental study in yeast has shown that this variant does not impair the transcriptional transactivation activity of the TP53 protein (PMID: 12826609). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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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