ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.266C>T (p.Pro89Leu) (rs730881994)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000161019 SCV000211736 uncertain significance not provided 2014-07-25 criteria provided, single submitter clinical testing This variant is denoted TP53 c.266C>T at the cDNA level, p.Pro89Leu (P89L) at the protein level, and results in the change of a Proline to a Leucine (CCC>CTC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. TP53 Pro89Leu was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Proline and Leucine differ in some properties, this is considered a semi-conservative amino acid substitution. TP53 Pro89Leu occurs at a position that is variable across species and is located in region of interaction with WWOX (UniProt). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether TP53 Pro89Leu is a pathogenic variant or a benign variant
Invitae RCV000560488 SCV000629797 uncertain significance Li-Fraumeni syndrome 2017-02-09 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 89 of the TP53 protein (p.Pro89Leu). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in the germline of individuals with a TP53-related disease. ClinVar contains an entry for this variant (Variation ID: 182923). Experimental studies have shown that this variant does not affect transactivation activity of the TP53 protein function in yeast-based assays (PMID: 12826609). In summary, this variant is a rare missense change that has been shown not to alter protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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