Submissions for variant NM_014795.4(ZEB2):c.1102C>T (p.Gln368Ter)

dbSNP: rs886041338

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000335345	SCV000329802	pathogenic	not provided	2016-05-05	criteria provided, single submitter	clinical testing	The Q368X nonsense variant in the ZEB2 gene has been reported previously in association with Mowat-Wilson syndrome (Dastot-Le Moal et al., 2007). The Q368X variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Therefore, we interpret Q368X to be a pathogenic variant.
Eurofins Ntd Llc (ga)	RCV000335345	SCV000330992	pathogenic	not provided	2016-06-20	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001800643	SCV002045650	pathogenic	Mowat-Wilson syndrome	2021-11-07	criteria provided, single submitter	clinical testing
Invitae	RCV001800643	SCV002222911	pathogenic	Mowat-Wilson syndrome	2022-07-26	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 280042). This premature translational stop signal has been observed in individual(s) with clinical features of Mowat-Wilson syndrome (PMID: 17203459, 30315573). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln368*) in the ZEB2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ZEB2 are known to be pathogenic (PMID: 16053902).