Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002031527 | SCV002309163 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with valine at codon 2085 of the ATM protein (p.Asp2085Val). The aspartic acid residue is weakly conserved and there is a large physicochemical difference between aspartic acid 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. 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. 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 | RCV002361417 | SCV002656443 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-12 | criteria provided, single submitter | clinical testing | The p.D2085V variant (also known as c.6254A>T), located in coding exon 42 of the ATM gene, results from an A to T substitution at nucleotide position 6254. The aspartic acid at codon 2085 is replaced by valine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |