Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000220936 | SCV000276574 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-21 | criteria provided, single submitter | clinical testing | The p.I1422T variant (also known as c.4265T>C), located in coding exon 28 of the ATM gene, results from a T to C substitution at nucleotide position 4265. The isoleucine at codon 1422 is replaced by threonine, an amino acid with similar properties. This variant was reported in 1/5560 prostate cancer cases and in 0/3353 controls of European ancestry (Karlsson Q et al. Eur Urol Oncol, 2021 08;4:570-579). 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. |
| Color Diagnostics, |
RCV000220936 | SCV000682192 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-12-09 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000797213 | SCV000936760 | uncertain significance | Ataxia-telangiectasia syndrome | 2022-02-24 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1422 of the ATM protein (p.Ile1422Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with prostate cancer (PMID: 33436325). ClinVar contains an entry for this variant (Variation ID: 232436). 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. |
| Sema4, |
RCV000220936 | SCV002534612 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-31 | criteria provided, single submitter | curation | |
| Baylor Genetics | RCV003462497 | SCV004213924 | uncertain significance | Familial cancer of breast | 2022-02-21 | criteria provided, single submitter | clinical testing |