Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000159642 | SCV000209631 | uncertain significance | not provided | 2024-03-01 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 23532176) |
| Labcorp Genetics |
RCV001857581 | SCV002304846 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-06-23 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with glycine at codon 2215 of the ATM protein (p.Ser2215Gly). The serine residue is moderately conserved and there is a small physicochemical difference between serine and glycine. 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: 181883). 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. |
| Ambry Genetics | RCV002362846 | SCV002664568 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-12-27 | criteria provided, single submitter | clinical testing | The p.S2215G variant (also known as c.6643A>G), located in coding exon 45 of the ATM gene, results from an A to G substitution at nucleotide position 6643. The serine at codon 2215 is replaced by glycine, an amino acid with similar properties. This amino acid position is 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. |