Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002036476 | SCV002311316 | uncertain significance | EGFR-related lung cancer | 2023-10-30 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 776 of the EGFR protein (p.Arg776Cys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with EGFR-related conditions. ClinVar contains an entry for this variant (Variation ID: 1523057). 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 EGFR protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change does not substantially affect EGFR function (PMID: 19147750). 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. |
Key Laboratory of Carcinogenesis and Cancer Invasion, |
RCV004011175 | SCV004042716 | likely pathogenic | Lung adenocarcinoma | no assertion criteria provided | clinical testing |