ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.472C>G (p.Arg158Gly)

dbSNP: rs587780068
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001061572 SCV001226320 pathogenic Li-Fraumeni syndrome 2024-07-21 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 158 of the TP53 protein (p.Arg158Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Li-Fraumeni syndrome (PMID: 10864200, 21339461). ClinVar contains an entry for this variant (Variation ID: 856171). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is expected to disrupt TP53 function with a positive predictive value of 97.5%. Experimental studies have shown that this missense change affects TP53 function (PMID: 2134334, 9472631, 12826609). This variant disrupts the p.His158 amino acid residue in TP53. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17606709, 18685109, 20522432, 21601526, 25584008). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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