ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.1136G>T (p.Arg379Leu) (rs863224682)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000219990 SCV000275804 uncertain significance Hereditary cancer-predisposing syndrome 2017-03-09 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Integrated Genetics/Laboratory Corporation of America RCV000590314 SCV000697426 uncertain significance not provided 2017-07-21 criteria provided, single submitter clinical testing Variant summary: The TP53 c.1136G>T (p.Arg379Leu) variant involves the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a damaging outcome for this variant. This variant is absent in 121384 control chromosomes. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000199273 SCV000254625 uncertain significance Li-Fraumeni syndrome 2018-09-11 criteria provided, single submitter clinical testing This sequence change replaces arginine with leucine at codon 379 of the TP53 protein (p.Arg379Leu). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine 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: 216463). An experimental study in yeast has shown that this variant partially impairs the transcriptional transactivation activity of the TP53 protein (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.

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