Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001052811 | SCV001217039 | uncertain significance | Li-Fraumeni syndrome | 2021-09-19 | 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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on TP53 function (PMID: 12826609). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with TP53-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with serine at codon 364 of the TP53 protein (p.Ala364Ser). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and serine. |
| Ambry Genetics | RCV002445283 | SCV002734207 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-21 | criteria provided, single submitter | clinical testing | The p.A364S variant (also known as c.1090G>T), located in coding exon 9 of the TP53 gene, results from a G to T substitution at nucleotide position 1090. The alanine at codon 364 is replaced by serine, an amino acid with similar properties. This variant is reported to have partially 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 has no dominant negative effect (Giacomelli AO et al. Nat. Genet. 2018 Oct;50:1381-1387). This amino acid position is not well 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. |