Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001247837 | SCV001421284 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with alanine at codon 274 of the ATM protein (p.Ser274Ala). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and alanine. This variant is not present in population databases (ExAC no frequency). 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine 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. |
| Ambry Genetics | RCV002430048 | SCV002679735 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-31 | criteria provided, single submitter | clinical testing | The p.S274A variant (also known as c.820T>G), located in coding exon 6 of the ATM gene, results from a T to G substitution at nucleotide position 820. The serine at codon 274 is replaced by alanine, an amino acid with 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. |