ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.890A>G (p.His297Arg)

dbSNP: rs876659477
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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 RCV000214757 SCV000276000 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-02 criteria provided, single submitter clinical testing The p.H297R variant (also known as c.890A>G), located in coding exon 7 of the TP53 gene, results from an A to G substitution at nucleotide position 890. The histidine at codon 297 is replaced by arginine, an amino acid with highly similar properties. This variant is reported to have functional transactivation in yeast based assays (Kato S et al. Proc. Natl. Acad. Sci. USA. 2003 Jul;100:8424-9). Studies conducted in human cell lines indicate this alteration is proficient at growth suppression and has no dominant negative effect (Giacomelli AO et al. Nat Genet, 2018 10;50:1381-1387). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV002515650 SCV003340345 uncertain significance Li-Fraumeni syndrome 2024-08-12 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 297 of the TP53 protein (p.His297Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 231990). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is not expected to disrupt TP53 function with a negative predictive value of 97.5%. 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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