Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000469538 | SCV000563876 | likely pathogenic | Ataxia-telangiectasia syndrome | 2016-11-19 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 48-51 of the ATM gene. This leads to an in-frame deletion, preserving the integrity of the reading frame. While this particular deletion has not been reported in the literature, gross deletions and loss-of-function variants in ATM are known to be pathogenic (PMID: 25614872, 23807571). This gross deletion eliminates 217 amino acid residues from the ATM FAT domain, which is involved in scaffolding the kinase domain (PMID: 23532176, 25460276). Loss of this domain is expected to disrupt normal ATM protein functions such as cell cycle regulation, DNA damage response, and maintenance of genome stability (PMID: 18813293, 23532176), but this prediction has not been confirmed by published functional studies. In summary, this deletion is expected to disrupt ATM protein function. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |