Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000164436 | SCV000215075 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-06-11 | criteria provided, single submitter | clinical testing | The p.G2863V variant (also known as c.8588G>T), located in coding exon 58 of the ATM gene, results from a G to T substitution at nucleotide position 8588. The glycine at codon 2863 is replaced by valine, an amino acid with dissimilar 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. |
| Labcorp Genetics |
RCV001850297 | SCV002113556 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with valine at codon 2863 of the ATM protein (p.Gly2863Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 185078). 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 ATM 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. |