Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001944979 | SCV002130396 | uncertain significance | EGFR-related lung cancer | 2024-02-26 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 556 of the EGFR protein (p.Ile556Val). 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: 1367065). 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 EGFR protein function with a negative 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 | RCV004946787 | SCV005574762 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-12-06 | criteria provided, single submitter | clinical testing | The p.I556V variant (also known as c.1666A>G), located in coding exon 14 of the EGFR gene, results from an A to G substitution at nucleotide position 1666. The isoleucine at codon 556 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |