Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001026003 | SCV001188302 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-10-28 | criteria provided, single submitter | clinical testing | The p.M2357T variant (also known as c.7070T>C), located in coding exon 47 of the ATM gene, results from a T to C substitution at nucleotide position 7070. The methionine at codon 2357 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001862349 | SCV002252457 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-06-18 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with threonine at codon 2357 of the ATM protein (p.Met2357Thr). The methionine residue is moderately conserved and there is a moderate physicochemical difference between methionine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 826818). 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. 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. |