Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000708135 | SCV000837245 | likely pathogenic | Ataxia-telangiectasia syndrome | 2020-05-27 | criteria provided, single submitter | clinical testing | This variant results in a copy number gain of the genomic region encompassing exon(s) 48-61 of the ATM gene. While the exact position of this variant cannot be determined from the data, sub-genic copy number gains are generally in tandem (PMID: 25640679). This variant is predicted to be in-frame, and likely preserves the integrity of the reading frame. This variant has been observed in individual(s) with ataxia-telangiectasia (Invitae). It has also been observed to segregate with disease in related individuals. This variant disrupts the kinase domain of the ATM protein, which is required for DNA damage response (PMID: 24667671). While functional studies have not been performed to directly test the effect of this variant on ATM protein function, this suggests that disruption of this region of the protein is causative of disease. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |