ClinVar Miner

Submissions for variant NM_001126112.2(TP53):c.541C>A (p.Arg181Ser) (rs587782596)

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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 RCV000222957 SCV000274425 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-07 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Color RCV000222957 SCV000686748 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-09 criteria provided, single submitter clinical testing
Invitae RCV000799329 SCV000938988 uncertain significance Li-Fraumeni syndrome 2018-10-22 criteria provided, single submitter clinical testing This sequence change replaces arginine with serine at codon 181 of the TP53 protein (p.Arg181Ser). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and serine. 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: 230764). An experimental study in yeast has shown that this variant partially impairs the transcriptional transactivation activity of the TP53 protein (PMID: 12826609). This variant disrupts the p.Arg181 amino acid residue in TP53. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 1581912, 17606709, 23484829, 27501770, 8308926, 15925506), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. 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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