Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001233871 | SCV001406485 | uncertain significance | EGFR-related lung cancer | 2025-01-11 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 147 of the EGFR protein (p.Ala147Thr). This variant is present in population databases (rs532655845, gnomAD 0.01%). 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: 960359). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The threonine 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 | RCV004951395 | SCV005579624 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-11-08 | criteria provided, single submitter | clinical testing | The p.A147T variant (also known as c.439G>A), located in coding exon 4 of the EGFR gene, results from a G to A substitution at nucleotide position 439. The alanine at codon 147 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. 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. |