Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001055197 | SCV001219573 | uncertain significance | Li-Fraumeni syndrome | 2023-07-17 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 850916). This sequence change replaces valine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 225 of the TP53 protein (p.Val225Asp). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
| Ambry Genetics | RCV002374925 | SCV002667867 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-04-10 | criteria provided, single submitter | clinical testing | The p.V225D variant (also known as c.674T>A), located in coding exon 6 of the TP53 gene, results from a T to A substitution at nucleotide position 674. The valine at codon 225 is replaced by aspartic acid, an amino acid with highly dissimilar properties. This variant is in the DNA binding domain of the TP53 protein and is reported to have transactivation greater than wild type in yeast based assays (IARC TP53 database: Kato S et al. Proc. Natl. Acad. Sci. USA 2003 Jul;100:8424-9). Studies conducted in human cell lines indicate this alteration remains proficient 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 well 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. |