Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000219396 | SCV000276691 | likely benign | Hereditary cancer-predisposing syndrome | 2024-07-29 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Labcorp Genetics |
RCV000695904 | SCV000824430 | uncertain significance | Ataxia-telangiectasia syndrome | 2025-01-27 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 1128 of the ATM protein (p.Gln1128Glu). This variant is present in population databases (no rsID available, 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: 232533). 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) indicates that this missense variant is not expected to disrupt ATM protein function with a negative predictive value of 95%. 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. |
| Color Diagnostics, |
RCV000219396 | SCV000904819 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-05 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamine with glutamic acid at codon 1128 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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 been identified in 1/250912 chromosomes 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. |
| Genome- |
RCV000695904 | SCV001781327 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-07-14 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV000695904 | SCV002080328 | uncertain significance | Ataxia-telangiectasia syndrome | 2020-07-15 | no assertion criteria provided | clinical testing |