Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001309869 | SCV001499382 | uncertain significance | Ataxia-telangiectasia syndrome | 2022-05-27 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 2896 of the ATM protein (p.Gln2896Pro). 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 expected to disrupt ATM protein function. ClinVar contains an entry for this variant (Variation ID: 1011982). 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). |
| 3billion | RCV001309869 | SCV002012340 | uncertain significance | Ataxia-telangiectasia syndrome | 2024-07-30 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v4.0.0 dataset. The majority of the known disease-causing variants of this gene are variants expected to result in premature termination of the protein. In silico tool predictions suggest damaging effect of the variant on gene or gene product [REVEL: 0.92 (>=0.6); 3Cnet: 0.99 (>=0.6)]. The variant has been reported as of uncertain significance (ClinVar ID: VCV001011982; 3billion dataset). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline. |