ClinVar Miner

Submissions for variant NM_032444.4(SLX4):c.5229dup (p.Gln1744fs) (rs781479923)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000531680 SCV000626448 likely pathogenic Fanconi anemia 2017-07-28 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the SLX4 gene (p.Gln1744Alafs*34). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 91 amino acids of the SLX4 protein. This variant is present in population databases (rs781479923, ExAC 0.002%). This variant has been reported in an individual affected with breast cancer (PMID: 24733792). No experimental studies have been performed to test the effects of this variant on SLX4 protein function or stability. However, it is expected to result in the disruption of the last 91 amino acids (Gln1744-Asn1834) of the SLX4 protein. This removes most of the SLX1 interaction domain, which has been shown to be critical for SLX1-SLX4 complexing, and therefore will affect their Holliday junction resolvase and 5'-flap endonuclease activities (PMID: 19596235, 19596236). 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.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001091529 SCV001247644 pathogenic not provided 2017-08-01 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.