ClinVar Miner

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

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785467 SCV000924039 likely pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research
Invitae RCV000633368 SCV000754590 pathogenic Li-Fraumeni syndrome 2017-12-18 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). This variant has been reported in an individual affected with liposarcoma and pancreatic adenocarcinoma (PMID: 27501770). This variant is also known as E9+1 G>A in the literature. A different variant affecting this nucleotide (c.993+1delG, also known as IVS9+1delG) giving rise to G>T change at the +1 donor splice site has been determined to be pathogenic (PMID: 10980596). This suggests that this nucleotide is important for normal RNA splicing, and that other variants at this position may also be pathogenic. 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 RCV000786816 SCV000925708 not provided not provided no assertion provided in vitro

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