ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.375+1G>T

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000804919 SCV000944857 pathogenic Li-Fraumeni syndrome 2018-10-15 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 4 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 in individuals affected with clinical features of Li-Fraumeni syndrome (PMID: 17224268, 7887414, Invitae). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
MutSpliceDB: a database of splice sites variants effects on splicing,NIH RCV000786840 SCV000925736 not provided not provided no assertion provided in vitro

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