Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000222174 | SCV000275747 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-10 | criteria provided, single submitter | clinical testing | The p.I1476M variant (also known as c.4428C>G), located in coding exon 28 of the ATM gene, results from a C to G substitution at nucleotide position 4428. The isoleucine at codon 1476 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is 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. |
| Labcorp Genetics |
RCV001307358 | SCV001496768 | uncertain significance | Ataxia-telangiectasia syndrome | 2022-01-26 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1476 of the ATM protein (p.Ile1476Met). This variant is not present in population databases (gnomAD no frequency). 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: 231794). 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. |
| Baylor Genetics | RCV004567575 | SCV005055904 | uncertain significance | Familial cancer of breast | 2024-03-24 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV004772869 | SCV005385802 | uncertain significance | not provided | 2024-01-31 | 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 |