Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000166182 | SCV000216957 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-29 | criteria provided, single submitter | clinical testing | The p.E1139Q variant (also known as c.3415G>C), located in coding exon 23 of the ATM gene, results from a G to C substitution at nucleotide position 3415. The glutamic acid at codon 1139 is replaced by glutamine, an amino acid with highly similar properties. 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. |
| Labcorp Genetics |
RCV001070498 | SCV001235745 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-12-14 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 1139 of the ATM protein (p.Glu1139Gln). 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: 186567). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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 |
RCV001762384 | SCV001991133 | uncertain significance | not provided | 2019-05-30 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge |
| Baylor Genetics | RCV004567297 | SCV005057132 | uncertain significance | Familial cancer of breast | 2023-12-20 | criteria provided, single submitter | clinical testing |