Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000227092 | SCV000282921 | uncertain significance | Ataxia-telangiectasia syndrome | 2022-09-26 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1040 of the ATM protein (p.Met1040Ile). This variant is present in population databases (rs781519408, gnomAD 0.0009%). 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: 236698). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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 | RCV002321848 | SCV002607928 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-09 | criteria provided, single submitter | clinical testing | The p.M1040I variant (also known as c.3120G>C), located in coding exon 20 of the ATM gene, results from a G to C substitution at nucleotide position 3120. The methionine at codon 1040 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |