ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.993+1G>C (rs11575997)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000429174 SCV000517237 pathogenic not provided 2015-05-20 criteria provided, single submitter clinical testing This TP53 c.993+1G>C variant destroys a canonical splicedonor site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject tononsense-mediated mRNA decay or to an abnormal protein product. TP53 993+1G>C has been reported as asomatic variant, observed in both ovarian and liver tumors (COSMIC). We consider this variant to be pathogenic.
Invitae RCV000799825 SCV000939507 pathogenic Li-Fraumeni syndrome 2018-12-11 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 9 of the TP53 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed to segregate with Li Fraumeni syndrome in a family (PMID: 10980596). ClinVar contains an entry for this variant (Variation ID: 379801). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432). For these reasons, this variant has been classified as Pathogenic.

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