Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001011530 | SCV001171861 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-12-11 | criteria provided, single submitter | clinical testing | The p.C489G variant (also known as c.1465T>G), located in coding exon 9 of the ATM gene, results from a T to G substitution at nucleotide position 1465. The cysteine at codon 489 is replaced by glycine, an amino acid with highly dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001218615 | SCV001390503 | uncertain significance | Ataxia-telangiectasia syndrome | 2022-08-06 | criteria provided, single submitter | clinical testing | 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. 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 ATM protein function. ClinVar contains an entry for this variant (Variation ID: 819191). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 489 of the ATM protein (p.Cys489Gly). |