ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.11C>T (p.Pro4Leu) (rs878854064)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000229754 SCV000285174 uncertain significance Li-Fraumeni syndrome 2018-07-16 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 4 of the TP53 protein (p.Pro4Leu). 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). This variant has not been reported in the literature in individuals with TP53-related disease. ClinVar contains an entry for this variant (Variation ID: 237941). Experimental studies have shown that this variant does not affect TP53 transactivation activity in yeast-based assays (PMID: 12826609), In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000571530 SCV000672384 uncertain significance Hereditary cancer-predisposing syndrome 2017-12-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Counsyl RCV000662489 SCV000784994 uncertain significance Li-Fraumeni syndrome 1 2017-03-03 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759369 SCV000888659 uncertain significance not provided 2018-06-27 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000780782 SCV000918324 uncertain significance not specified 2018-01-29 criteria provided, single submitter clinical testing Variant summary: TP53 c.11C>T (p.Pro4Leu) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 245472 control chromosomes. The variant c.11C>T has been reported in the literature as a somatic variant in breast cancer (Ellis_TP53_Nature_2012; COSMIC). This report does not provide unequivocal conclusions about an association of the variant with Li-Fraumeni Syndrome. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, both of which classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance until additional clinical and functional data is available.

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