ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.328C>A (p.Arg110Ser) (rs587781371)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129184 SCV000183919 uncertain significance Hereditary cancer-predisposing syndrome 2017-04-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000461586 SCV000545337 uncertain significance Li-Fraumeni syndrome 2018-05-18 criteria provided, single submitter clinical testing This sequence change replaces arginine with serine at codon 110 of the TP53 protein (p.Arg110Ser). The arginine residue is moderately 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: 140921). Experimental studies have shown that this missense change disrupts p53 transactivation activity in vitro (PMID: 12826609). A different missense substitution at this codon (p.Arg110Pro) has been determined to be pathogenic (PMID: 1552135, 23894400, 12826609, 23897043). 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.

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