ClinVar

Description

This variant is denoted TP53 c.845G>A at the cDNA level, p.Arg282Gln (R282Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGG>CAG). This variant was observed in a patient with neuroblastoma and was reportedly inherited from one of her parents, but the family history was not suggestive of Li-Fraumeni syndrome (Chompret 2000). Functional analyses have found that TP53 Arg282Gln results in variedtransactivation or repression abilities across p53 responsive elements (Andreotti 2011, Resnick 2003, Monti 2011, Campomenosi 2001), and this variant is reported as having partially functional transactivation in the International Agency for Research on Cancer TP53 database based on functional assays by Kato et al. (2003). TP53 Arg282Gln was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Arginine and Glutamine differ in some properties, this is considered a semi-conservative amino acid substitution. TP53 Arg282Gln occurs at a position that is not conserved and is located in the DNA binding domain (Bode 2004). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether TP53 Arg282Gln is pathogenic or benign. We consider it to be a variant of uncertain significance