ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.329G>T (p.Arg110Leu) (rs11540654)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000473145 SCV000545344 pathogenic Li-Fraumeni syndrome 2018-07-17 criteria provided, single submitter clinical testing This sequence change replaces arginine with leucine at codon 110 of the TP53 protein (p.Arg110Leu). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is present in population databases (rs11540654, ExAC 0.006%). This variant has been reported in individuals affected with Li-Fraumeni syndrome (LFS) or suspected LFS (PMID: 9667734, 18511570, Invitae). It was also observed to be de novo in an individual affected with LFS-associated cancers (Invitae). ClinVar contains an entry for this variant (Variation ID: 406597). Experimental studies have shown that this missense change disrupts TP53 protein function (PMID: 9290701, 17724467, 16778209, 24076587, 21445056). A different missense substitution at this codon (p.Arg110Pro) has been determined to be pathogenic (PMID: 12826609, 21552135, 23894400, 23897043, 24076587). 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.
Ambry Genetics RCV000492590 SCV000581121 likely pathogenic Hereditary cancer-predisposing syndrome 2015-11-05 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Deficient protein function in appropriate functional assay(s),Well-characterized mutation at same position,Rarity in general population databases (dbsnp, esp, 1000 genomes),Other strong data supporting pathogenic classification
Color RCV000492590 SCV000691588 likely pathogenic Hereditary cancer-predisposing syndrome 2018-04-27 criteria provided, single submitter clinical testing
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785348 SCV000923916 likely pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research

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