ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.587G>T (p.Arg196Leu)

dbSNP: rs483352697
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001024636 SCV001186684 uncertain significance Hereditary cancer-predisposing syndrome 2018-01-04 criteria provided, single submitter clinical testing The p.R196L variant (also known as c.587G>T), located in coding exon 5 of the TP53 gene, results from a G to T substitution at nucleotide position 587. The arginine at codon 196 is replaced by leucine, an amino acid with dissimilar properties. This alteration has been reported as a somatic mutation two times in various tumors, but not as a germline mutation by the IARC TP53 database (Petitjean A et al. IARC TP53 database [version R17, November 2013]. Hum. Mutat. 2007 Jun;28:622-9). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Department of Pediatrics, Memorial Sloan Kettering Cancer Center RCV001523825 SCV001478187 likely pathogenic Li-Fraumeni syndrome 1 2020-12-15 criteria provided, single submitter research
Color Diagnostics, LLC DBA Color Health RCV001024636 SCV001735580 uncertain significance Hereditary cancer-predisposing syndrome 2024-01-04 criteria provided, single submitter clinical testing This missense variant replaces arginine with leucine at codon 196 of the TP53 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have shown that this variant has a neutral effect on TP53 protein function (PMID: 29979965, 30224644). To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Invitae RCV002514536 SCV003317131 uncertain significance Li-Fraumeni syndrome 2022-04-05 criteria provided, single submitter clinical testing 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. Advanced modeling of experimental studies (such as gene expression, population dynamics, functional pathways, and cell-cycle effects in cell culture) performed at Invitae indicates that this missense variant is expected to disrupt TP53 protein function. ClinVar contains an entry for this variant (Variation ID: 100814). This variant has not been reported in the literature in individuals affected with TP53-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 196 of the TP53 protein (p.Arg196Leu).
Richard Lifton Laboratory, Yale University School of Medicine RCV000087172 SCV000120034 unknown not provided flagged submission not provided Converted during submission to Uncertain significance.
Richard Lifton Laboratory, Yale University School of Medicine RCV000087172 SCV000155137 probable-pathogenic not provided no assertion criteria provided not provided Converted during submission to Likely pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.