Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000562982 | SCV000668146 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-08-03 | criteria provided, single submitter | clinical testing | The p.G774D variant (also known as c.2321G>A), located in coding exon 14 of the ATM gene, results from a G to A substitution at nucleotide position 2321. The glycine at codon 774 is replaced by aspartic acid, an amino acid with similar properties. This amino acid position is poorly 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. |
| Color | RCV000562982 | SCV000911844 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-01-27 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001049979 | SCV001214063 | uncertain significance | Ataxia-telangiectasia syndrome | 2019-10-20 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with aspartic acid at codon 774 of the ATM protein (p.Gly774Asp). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. 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. ClinVar contains an entry for this variant (Variation ID: 482746). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The aspartic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |