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

dbSNP: rs781479923

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000531680	SCV000626448	likely pathogenic	Fanconi anemia	2021-06-13	criteria provided, single submitter	clinical testing	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). 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. 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. 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).
CeGaT Center for Human Genetics Tuebingen	RCV001091529	SCV001247644	pathogenic	not provided	2017-08-01	criteria provided, single submitter	clinical testing