Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001055027 | SCV001219391 | uncertain significance | Li-Fraumeni syndrome | 2021-02-04 | criteria provided, single submitter | clinical testing | Experimental studies have shown that this variant does not substantially affect TP53 protein function (PMID: 12826609, 30224644). 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. 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 not expected to disrupt TP53 protein function. This variant has not been reported in the literature in individuals with TP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 850781). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with lysine at codon 51 of the TP53 protein (p.Glu51Lys). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and lysine. |