Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000569049 | SCV000660788 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-08-02 | criteria provided, single submitter | clinical testing | The p.K578Q variant (also known as c.1732A>C), located in coding exon 10 of the ATM gene, results from an A to C substitution at nucleotide position 1732. The lysine at codon 578 is replaced by glutamine, an amino acid with 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. |
| Color Diagnostics, |
RCV000569049 | SCV001339890 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-05 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with glutamine at codon 578 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 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 |
RCV001858071 | SCV002305749 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-08-02 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 479107). 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 not 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 (ExAC no frequency). This sequence change replaces lysine with glutamine at codon 578 of the ATM protein (p.Lys578Gln). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and glutamine. |