Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001348973 | SCV001543300 | uncertain significance | Ataxia-telangiectasia syndrome | 2020-06-13 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with proline at codon 1309 of the ATM protein (p.Ala1309Pro). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ATM-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 | RCV002377481 | SCV002624917 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-14 | criteria provided, single submitter | clinical testing | The p.A1309P variant (also known as c.3925G>C), located in coding exon 25 of the ATM gene, results from a G to C substitution at nucleotide position 3925. The alanine at codon 1309 is replaced by proline, 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. |