Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000465003 | SCV000545346 | uncertain significance | Li-Fraumeni syndrome | 2021-09-23 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with serine at codon 249 of the TP53 protein (p.Arg249Ser). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and serine. This variant is not present in population databases (ExAC no frequency). 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. Experimental studies have shown that this missense change affects TP53 function (PMID: 9405613, 12826609, 15060172, 15703170, 15982667, 18477611, 20538734). 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: 406598). This variant has not been reported in the literature in individuals affected with TP53-related conditions. |
Myriad Genetics, |
RCV004022606 | SCV004933454 | likely pathogenic | Li-Fraumeni syndrome 1 | 2024-02-16 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 8001119, 8843196, 12509279, 29979965]. This variant is expected to disrupt protein structure [Myriad internal data]. |