ClinVar Miner

Submissions for variant NM_005228.5(EGFR):c.2386G>A (p.Gly796Ser)

gnomAD frequency: 0.00001  dbSNP: rs754426793
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001366717 SCV001563030 uncertain significance EGFR-related lung cancer 2024-09-03 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 796 of the EGFR protein (p.Gly796Ser). This variant is present in population databases (rs754426793, gnomAD 0.01%). This missense change has been observed in individual(s) with squamous cell carcinoma of the head and neck (PMID: 18528899). ClinVar contains an entry for this variant (Variation ID: 1057685). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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 affects EGFR function (PMID: 18193092). 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.
CeGaT Center for Human Genetics Tuebingen RCV001531041 SCV001745986 likely pathogenic not provided 2021-04-01 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001531041 SCV004221885 uncertain significance not provided 2023-06-30 criteria provided, single submitter clinical testing In the published literature, this variant has been reported in individuals with squamous cell carcinoma of the head and neck (PMID: 18528899 (2008)). In vitro expression of this variant results in increased cell proliferation, invasion and EGFR downstream signaling associated with cancer progression (PMID: 18193092 (2008)). The frequency of this variant in the general population, 0.000012 (3/251474 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Additional analysis using software algorithms for the prediction of the effect of nucleotide changes on EGFR mRNA splicing yielded predictions that this variant may result in the gain of a cryptic splice site without affecting the natural splice sites . Based on the available information, we are unable to determine the clinical significance of this variant.
Fulgent Genetics, Fulgent Genetics RCV005038142 SCV005668420 uncertain significance Inflammatory skin and bowel disease, neonatal, 2; Lung cancer 2024-02-18 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.