Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001052031 | SCV001216220 | uncertain significance | EGFR-related lung cancer | 2023-11-29 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 109 of the EGFR protein (p.Gly109Ala). This variant is present in population databases (rs145113601, gnomAD 0.03%). 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: 848304). 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%. 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. |
| Ambry Genetics | RCV004950180 | SCV005579646 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-10-28 | criteria provided, single submitter | clinical testing | The p.G109A variant (also known as c.326G>C), located in coding exon 3 of the EGFR gene, results from a G to C substitution at nucleotide position 326. The glycine at codon 109 is replaced by alanine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |