Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001026129 | SCV001188450 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2019-12-11 | criteria provided, single submitter | clinical testing | The p.S240R variant (also known as c.718A>C), located in coding exon 6 of the TP53 gene, results from an A to C substitution at nucleotide position 718. The serine at codon 240 is replaced by arginine, an amino acid with dissimilar properties. This variant is in the DNA binding domain of the TP53 protein and is reported to have partial loss of transactivation 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 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). Though this exact alteration has not been published in the literature, another alteration at this same codon (p.S240G/c.718A>G) has been reported in an individual with Li-Fraumeni syndrome (Villani A et al. Lancet Oncol. 2016 Sep;17(9):1295-305). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |