ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.542G>T (p.Arg181Leu) (rs397514495)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000692266 SCV000820080 uncertain significance Li-Fraumeni syndrome 2018-03-14 criteria provided, single submitter clinical testing This sequence change replaces arginine with leucine at codon 181 of the TP53 protein (p.Arg181Leu). The arginine residue is highly 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 been reported in an individual affected with glioma and anaplastic astrocytoma (PMID: 8308926). ClinVar contains an entry for this variant (Variation ID: 39420). Experimental studies have shown that this missense change partially affects the transcriptional transactivation activity, DNA complex stability, apoptosis activity and expression of MDM2 (PMID: 21343334, 17606709, 8756654, 10871862, 20471942). The clinical significance of this finding is uncertain. Different missense substitutions at this codon (p.Arg181His and p.Arg181Cys) have been determined to be pathogenic (PMID: 20128691, 21343334, 11429705, 21059199, 1581912, 17606709). This suggests that the arginine residue is critical for TP53 protein function and that other missense substitutions at this position may also be pathogenic. 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.
OMIM RCV000032610 SCV000056364 risk factor Glioma susceptibility 1 1994-03-02 no assertion criteria provided literature only

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