Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000535472 | SCV000622573 | uncertain significance | Ataxia-telangiectasia syndrome | 2022-02-22 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 1743 of the ATM protein (p.Thr1743Ala). This variant is present in population databases (rs758924620, gnomAD 0.0009%). 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. This variant disrupts the p.Thr1743 amino acid residue in ATM. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9463314, 19147735, 19431188, 21792198, 31921190). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 453566). This variant has not been reported in the literature in individuals affected with ATM-related conditions. |
| Color Diagnostics, |
RCV000579805 | SCV000682256 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-22 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000579805 | SCV002642046 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-25 | criteria provided, single submitter | clinical testing | The p.T1743A variant (also known as c.5227A>G), located in coding exon 34 of the ATM gene, results from an A to G substitution at nucleotide position 5227. The threonine at codon 1743 is replaced by alanine, an amino acid with similar properties. This alteration has been reported with a carrier frequency of 0.00013 in 7636 unselected prostate cancer patients and was not identified in 12366 male controls of Japanese ancestry (Momozawa Y et al. J Natl Cancer Inst, 2020 Apr;112:369-376). This amino acid position is highly 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. |