Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001016337 | SCV001177284 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-05-07 | criteria provided, single submitter | clinical testing | The p.D899E variant (also known as c.2697C>G), located in coding exon 17 of the ATM gene, results from a C to G substitution at nucleotide position 2697. The aspartic acid at codon 899 is replaced by glutamic acid, an amino acid with highly similar properties. 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. |
| Invitae | RCV001271169 | SCV002218903 | uncertain significance | Ataxia-telangiectasia syndrome | 2022-10-26 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 899 of the ATM protein (p.Asp899Glu). 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: 821682). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. |
| Natera, |
RCV001271169 | SCV001452048 | uncertain significance | Ataxia-telangiectasia syndrome | 2020-09-16 | no assertion criteria provided | clinical testing |