Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001021233 | SCV001182820 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-09-28 | criteria provided, single submitter | clinical testing | The p.Q1276P variant (also known as c.3827A>C), located in coding exon 25 of the ATM gene, results from an A to C substitution at nucleotide position 3827. The glutamine at codon 1276 is replaced by proline, 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001344218 | SCV001538254 | uncertain significance | Ataxia-telangiectasia syndrome | 2022-07-06 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs770183693, gnomAD 0.0009%). This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 1276 of the ATM protein (p.Gln1276Pro). This variant has not been reported in the literature in individuals affected with ATM-related conditions. 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: 824264). |