Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001017048 | SCV001178071 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-10-03 | criteria provided, single submitter | clinical testing | The c.1024_1025delCGinsTT variant, also known as p.R342L, located in coding exon 9 of the TP53 gene, results from an in-frame deletion of CG and insertion of TT at nucleotide positions 1024 to 1025. This results in the substitution of the arginine residue for a leucine residue at codon 342, an amino acid with dissimilar properties. This variant is reported to have transactivation similar to 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 (Giacomelli AO et al. Nat. Genet. 2018 Oct;50:1381-1387). A similar alteration at this codon, p.R342P (c.1025G>C), has been identified in patients meeting LFS criteria or with LFS related tumors (Fiszer-Maliszewska L, Fam. Cancer 2009 ; 8(4):541-6; Etzold A et al., Fam. Cancer 2015 Mar; 14(1):161-5). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is conflicting at this time, the clinical significance of this alteration remains unclear. |