Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000628022 | SCV000748909 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-07-08 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 32 of the ATM protein (p.Arg32Leu). This variant is present in population databases (rs368161489, gnomAD 0.0009%). 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: 524321). 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 | RCV002385964 | SCV002695690 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-18 | criteria provided, single submitter | clinical testing | The p.R32L variant (also known as c.95G>T), located in coding exon 2 of the ATM gene, results from a G to T substitution at nucleotide position 95. The arginine at codon 32 is replaced by leucine, an amino acid with dissimilar properties. This variant was observed in an individual with early-onset breast cancer amongst a cohort of 1781 non-Ashkenazi Jewish individuals undergoing BRCA1/2 gene testing based on a personal history of breast cancer (Tung N et al. Cancer, 2015 Jan;121:25-33). 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. |
| Baylor Genetics | RCV003465372 | SCV004210044 | uncertain significance | Familial cancer of breast | 2023-08-11 | criteria provided, single submitter | clinical testing |