ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.672+1G>A (rs863224499)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000200333 SCV000253850 pathogenic Li-Fraumeni syndrome 2018-10-04 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 6 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). This variant has been observed in an individual affected with Li-Fraumeni-like syndrome (PMID: 22495821, 23409989). Experimental studies have shown that this variant affects mRNA splicing by inserting 6 amino acids between exons 6 and 7, resulting in altered TP53 protein DNA binding and transcriptional activity (PMID: 22495821). 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 RCV000786828 SCV000925722 not provided not provided no assertion provided in vitro

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