Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV000709182 | SCV000838545 | uncertain significance | Ataxia-telangiectasia syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000709182 | SCV001390516 | pathogenic | Ataxia-telangiectasia syndrome | 2023-10-30 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1592 of the ATM protein (p.Glu1592Gly). RNA analysis indicates that this missense change induces altered splicing and likely results in a shortened protein product. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 584790). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Studies have shown that this missense change results in skipping of 31, but is expected to preserve the integrity of the reading-frame (Invitae). Other variant(s) that result in skipping of exon 31 have been determined to be pathogenic (PMID: 2491181, 9497252, 9711876; Invitae). This suggests that this variant may also be clinically significant and likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |