Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001308546 | SCV001498001 | uncertain significance | Ataxia-telangiectasia syndrome | 2022-02-18 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1010842). 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. 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). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 2867 of the ATM protein (p.Gly2867Glu). |
| Color Diagnostics, |
RCV003584886 | SCV004361916 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-01 | criteria provided, single submitter | clinical testing | This missense variant replaces glycine with glutamic acid at codon 2867 of the ATM protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 hereditary cancer in the literature. This variant has been reported with the loss of the second ATM allele in chronic lymphocytic leukemia, and suggested to contribute tumor progression, but not initiation (PMID: 11756185, 12400598, 12958068, 16014569, 17968022, 21933854; DOI: 10.1182/blood.V116.21.2420.2420). 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. |