Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000814204 | SCV000954605 | uncertain significance | Ataxia-telangiectasia syndrome | 2022-06-09 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 691 of the ATM protein (p.Asp691His). This variant is present in population databases (rs762394404, 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: 657570). 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. |
| Gene |
RCV001772107 | SCV001992241 | uncertain significance | not provided | 2019-04-19 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 25600502) |
| Ambry Genetics | RCV002422812 | SCV002727712 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-14 | criteria provided, single submitter | clinical testing | The p.D691H variant (also known as c.2071G>C), located in coding exon 12 of the ATM gene, results from a G to C substitution at nucleotide position 2071. The aspartic acid at codon 691 is replaced by histidine, an amino acid with similar properties. This alteration was identified in a family with multiple cases of cutaneous melanoma. This family also was found to carry a RAD51B nonsense mutation (Wadt KA et al. Fam Cancer, 2015 Jun;14:337-40). This amino acid position is not 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. |