Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002587824 | SCV003489776 | uncertain significance | EGFR-related lung cancer | 2024-10-30 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 1148 of the EGFR protein (p.Asn1148Lys). This variant is present in population databases (rs778725594, gnomAD 0.0009%). 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: 2174368). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 | RCV004949001 | SCV005574745 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-12-02 | criteria provided, single submitter | clinical testing | The p.N1148K variant (also known as c.3444C>G), located in coding exon 28 of the EGFR gene, results from a C to G substitution at nucleotide position 3444. The asparagine at codon 1148 is replaced by lysine, an amino acid with 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. |