ClinVar Miner

Submissions for variant NM_001126112.2(TP53):c.761_763TCA[1] (p.Ile255del) (rs1064794309)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483701 SCV000568757 likely pathogenic not provided 2018-09-20 criteria provided, single submitter clinical testing The c.764_766delTCA variant in TP53 gene has previously been reported in at least one individual suspicious for Li-Fraumeni syndrome (Melhem-Bertrandt et al., 2012). The c.764_766delTCA variant is an in-frame deletion that results in the loss of a single Isoleucine residue, denoted p.I255del within the DNA binding domain (Bode et al., 2004). The residue removed by this deletion occurs at a position where amino acids with similar properties to Isoleucine are tolerated across species. Based on currently available evidence, c.764_766delTCA is a strong candidate for a pathogenic variant. However, the possibility it may be a rare benign variant cannot be excluded.
Invitae RCV000525682 SCV000629866 likely pathogenic Li-Fraumeni syndrome 2017-05-10 criteria provided, single submitter clinical testing This sequence change deletes 3 nucleotides from exon 7 of the TP53 mRNA (c.764_766delTCA). This leads to the deletion of 1 amino acid residue in the TP53 protein (p.Ile255del) but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with breast cancer and astrocytoma (PMID: 21761402). It has also been shown to arise de novo in an affected individual (Invitae). This variant is also known as c.763delATC in the literature. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acid is currently unknown. In summary, this variant is a rare in-frame deletion that has been observed in affected individuals. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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