Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000580017 | SCV000682245 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-05 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with glycine at codon 1682 of the ATM protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with ATM-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Labcorp Genetics |
RCV000817816 | SCV000958399 | uncertain significance | Ataxia-telangiectasia syndrome | 2024-12-24 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1682 of the ATM protein (p.Asp1682Gly). This variant is not present in population databases (gnomAD 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: 489553). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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 | RCV000580017 | SCV001185349 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-12-18 | criteria provided, single submitter | clinical testing | The p.D1682G variant (also known as c.5045A>G), located in coding exon 33 of the ATM gene, results from an A to G substitution at nucleotide position 5045. The aspartic acid at codon 1682 is replaced by glycine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. 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. |
| Gene |
RCV003441964 | SCV004169289 | uncertain significance | not provided | 2023-05-08 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |