Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001208957 | SCV001380374 | uncertain significance | Ataxia-telangiectasia syndrome | 2019-07-03 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with alanine at codon 2608 of the ATM protein (p.Thr2608Ala). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and alanine. This variant is not present in population databases (ExAC no frequency). 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 alanine 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. |
| Ambry Genetics | RCV004033751 | SCV005020154 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-10 | criteria provided, single submitter | clinical testing | The p.T2608A variant (also known as c.7822A>G), located in coding exon 52 of the ATM gene, results from an A to G substitution at nucleotide position 7822. The threonine at codon 2608 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |