Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002356518 | SCV002655403 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2020-08-18 | criteria provided, single submitter | clinical testing | The p.R213G variant (also known as c.637C>G), located in coding exon 5 of the TP53 gene, results from a C to G substitution at nucleotide position 637. The arginine at codon 213 is replaced by glycine, an amino acid with dissimilar properties. This variant is in the DNA binding domain of the TP53 protein and is reported to have loss of transactivation in yeast based assays (IARC TP53 database: Kato S et al. Proc. Natl. Acad. Sci. USA 2003 Jul;100:8424-9). Additional studies conducted in human cell lines indicate this alteration is deficient at growth suppression (Kotler E et al. Mol. Cell. 2018 Jul;71:178-190.e8; Giacomelli AO et al. Nat. Genet. 2018 Oct;50:1381-1387). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Labcorp Genetics |
RCV002524699 | SCV003317130 | uncertain significance | Li-Fraumeni syndrome | 2022-08-24 | 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: 376651). This missense change has been observed in individual(s) with precursor B-cell acute lymphoblastic leukemia (PMID: 33332384). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 213 of the TP53 protein (p.Arg213Gly). |
| Myriad Genetics, |
RCV004022237 | SCV004931963 | likely pathogenic | Li-Fraumeni syndrome 1 | 2024-02-15 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 29979965]. This variant is expected to disrupt protein structure [Myriad internal data]. |
| Department of Clinical Genetics, |
RCV002524699 | SCV005689578 | likely pathogenic | Li-Fraumeni syndrome | 2025-02-04 | criteria provided, single submitter | clinical testing | PM2_SUP; PS3; PP3_MOD |