ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.1060C>T (p.Gln354Ter) (rs755394212)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000531178 SCV000629769 likely pathogenic Li-Fraumeni syndrome 2017-11-29 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the TP53 gene (p.Gln354*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 39 amino acids of the TP53 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TP53-related disease. No experimental studies have been performed to test the effects of this specific variant on TP53 protein function. However, this variant deletes two amino acid residues from the tetramerization domain (residues 323-356) and all of the C-terminal regulatory domain (residues 363-393) of the TP53 protein. The C-terminal region of TP53 protein has been shown to be important for regulation, nuclear localization, DNA-binding, and transactivation activity (PMID: 22178617, 25794615, 26205489, 20932800). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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