ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.473G>T (p.Arg158Leu) (rs587782144)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000633348 SCV000754570 pathogenic Li-Fraumeni syndrome 2017-09-19 criteria provided, single submitter clinical testing This sequence change replaces arginine with leucine at codon 158 of the TP53 protein (p.Arg158Leu). 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  adrenocortical carcinoma (PMID: 25584008). Experimental studies using model organisms and mammalian cells have shown that this missense change disrupts TP53 protein function (PMID: 15037740, 16861262, 19756158, 25584008, 12725534). A different missense substitution at this codon (p.Arg158His) has been determined to be pathogenic (PMID: 17606709, 20522432, 25584008, 10486318, 23894400, 20455025). This suggests that the arginine residue is critical for TP53 protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.

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