Submissions for variant NM_014795.4(ZEB2):c.3206C>A (p.Ser1069Ter)

dbSNP: rs1553960778

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000579115	SCV000681144	pathogenic	not provided	2017-11-24	criteria provided, single submitter	clinical testing	The S1069X pathogenic variant in the ZEB2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function through protein truncation, as the last 146 amino acids are lost. The S1069X variant is not observed in large population cohorts (Lek et al., 2016).
Labcorp Genetics (formerly Invitae), Labcorp	RCV003611519	SCV004436998	pathogenic	Mowat-Wilson syndrome	2023-02-17	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser1069*) in the ZEB2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 146 amino acid(s) of the ZEB2 protein. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the ZEB2 protein in which other variant(s) (p.Gln1119Arg) have been determined to be pathogenic (PMID: 16688751). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 489157). This variant has not been reported in the literature in individuals affected with ZEB2-related conditions. This variant is not present in population databases (gnomAD no frequency).