ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.1140del (p.His380fs) (rs1555524108)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000537354 SCV000629778 uncertain significance Li-Fraumeni syndrome 2017-04-10 criteria provided, single submitter clinical testing This sequence change deletes 1 nucleotide from exon 11 of the TP53 mRNA (c.1140delT), causing a frameshift at codon 380 (p.His380Glnfs*42). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 14 amino acids of the TP53 protein, and to extend the protein by an additional 27 amino acids. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a TP53-related disease. This variant disrupts a portion of the C-terminal regulatory domain (residues 363-393) of TP53 that is necessary for full TP53 DNA binding and transactivation activity (PMID: 22178617, 25794615, 26205489). However, this particular variant has not been tested, and the clinical significance of this disruption is unknown. In summary, this variant is a novel frameshift in the final exon of TP53 with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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