Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000221942 | SCV000276159 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-06-05 | criteria provided, single submitter | clinical testing | The p.Q2590E variant (also known as c.7768C>G), located in coding exon 51 of the ATM gene, results from a C to G substitution at nucleotide position 7768. The glutamine at codon 2590 is replaced by glutamic acid, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6499 samples (12998 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 66000 alleles tested) in our clinical cohort. This amino acid position is not well conserved however, glutamine is a reference amino acid in several 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 variant remains unclear. |
| Labcorp Genetics |
RCV001853580 | SCV002146381 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-02-17 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with glutamic acid at codon 2590 of the ATM protein (p.Gln2590Glu). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and glutamic acid. 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. 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 glutamic 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. This variant has not been reported in the literature in individuals with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 232109). This variant is not present in population databases (ExAC no frequency). |