Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000469661 | SCV000546881 | uncertain significance | Ataxia-telangiectasia syndrome | 2022-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 1728 of the ATM protein (p.Lys1728Arg). This variant is present in population databases (no rsID available, gnomAD 0.007%). 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: 407577). 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. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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 | RCV000571264 | SCV000667996 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-14 | criteria provided, single submitter | clinical testing | The p.K1728R variant (also known as c.5183A>G), located in coding exon 34 of the ATM gene, results from an A to G substitution at nucleotide position 5183. The lysine at codon 1728 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Sema4, |
RCV000571264 | SCV002528298 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-07 | criteria provided, single submitter | curation | |
| Color Diagnostics, |
RCV000571264 | SCV004361019 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-07 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with arginine at codon 1728 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 been reported in individual affected with breast and/or ovarian cancer (PMID: 32068069) as well as in a healthy control (PMID: 33471991). This variant has been identified in 3/251156 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. |
| Baylor Genetics | RCV004567996 | SCV005056974 | uncertain significance | Familial cancer of breast | 2024-02-18 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV000469661 | SCV002080895 | uncertain significance | Ataxia-telangiectasia syndrome | 2020-12-13 | no assertion criteria provided | clinical testing |