Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001048155 | SCV001212145 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-08-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with glutamic acid at codon 912 of the ATM protein (p.Gln912Glu). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and glutamic acid. This variant is present in population databases (rs764409952, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with ATM-related conditions. 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. |
| Ambry Genetics | RCV002436587 | SCV002746104 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-01-21 | criteria provided, single submitter | clinical testing | The p.Q912E variant (also known as c.2734C>G), located in coding exon 17 of the ATM gene, results from a C to G substitution at nucleotide position 2734. The glutamine at codon 912 is replaced by glutamic acid, an amino acid with highly similar properties. This variant was detected in 1/77 Chinese patients diagnosed with esophageal squamous cell carcinoma (ESCC) (Deng J et al. Front Genet, 2019 Feb;10:47). 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004702601 | SCV005204856 | uncertain significance | not specified | 2024-06-10 | criteria provided, single submitter | clinical testing | Variant summary: ATM c.2734C>G (p.Gln912Glu) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251410 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2734C>G in individuals affected with Ataxia-Telangiectasia and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 845144). Based on the evidence outlined above, the variant was classified as uncertain significance. |