Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001369964 | SCV001566423 | uncertain significance | Ataxia-telangiectasia syndrome | 2022-02-27 | 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 1471 of the ATM protein (p.Thr1471Ala). 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: 1060523). 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. |
| Mendelics | RCV002246343 | SCV002517867 | uncertain significance | not specified | 2022-05-04 | criteria provided, single submitter | clinical testing | |
| KCCC/NGS Laboratory, |
RCV003237355 | SCV003936026 | uncertain significance | Familial cancer of breast | 2023-06-06 | criteria provided, single submitter | clinical testing | a variant of uncertain significance was detected in the ATM gene (p.Thr1471Ala). This sequence change replaces threonine with alanine at codon 1471 of the ATM protein (p.Thr1471Ala). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and alanine. 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. Insilico predictions show pathogenic computational verdict based on 9 pathogenic predictions from BayesDel_addAF, DANN, EIGEN, FATHMMMKL, M-CAP, MVP, MutationAssessor, MutationTaster and SIFT vs 3 benign predictions from DEOGEN2, LIST-S2 and PrimateAI. Therefore, it has been classified as a Variant of Uncertain Significance. Pathogenic/likely pathogenic mutations in the ATM gene cause susceptibility to breast cancer (OMIM 114480). |