ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.587G>T (p.Arg196Leu) (rs483352697)

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Total submissions: 5
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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 Health, Inc RCV001024636 SCV001735580 uncertain significance Hereditary cancer-predisposing syndrome 2020-10-13 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.
Richard Lifton Laboratory, Yale University School of Medicine RCV000087172 SCV000120034 unknown not provided no assertion criteria provided 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.

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