Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001056768 | SCV001221230 | uncertain significance | Li-Fraumeni syndrome | 2021-07-24 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with leucine at codon 267 of the TP53 protein (p.Arg267Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine. 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. This variant disrupts the p.Arg267 amino acid residue in TP53. Other variant(s) that disrupt this residue have been observed in individuals with TP53-related conditions (PMID: 25584008, 28573494, 29324801, 30588330; Invitae), which suggests that this may be a clinically significant amino acid residue. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on TP53 protein function (PMID: 12826609, 29979965, 30224644). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TP53 protein function. ClinVar contains an entry for this variant (Variation ID: 852206). 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). |