Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000227613 | SCV000283067 | uncertain significance | Ataxia-telangiectasia syndrome | 2019-07-19 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with threonine at codon 2648 of the ATM protein (p.Pro2648Thr). The proline residue is moderately conserved and there is a small physicochemical difference between proline and threonine. This variant has not been reported in the literature in individuals with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 236781). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). |
Mendelics | RCV000227613 | SCV000838604 | uncertain significance | Ataxia-telangiectasia syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV003362733 | SCV004053908 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-17 | criteria provided, single submitter | clinical testing | The p.P2648T variant (also known as c.7942C>A), located in coding exon 53 of the ATM gene, results from a C to A substitution at nucleotide position 7942. The proline at codon 2648 is replaced by threonine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |