Submissions for variant NM_016373.4(WWOX):c.583G>T (p.Glu195Ter)

dbSNP: rs1567542020

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000688699	SCV000816321	pathogenic	Developmental and epileptic encephalopathy, 1; Autosomal recessive spinocerebellar ataxia 12	2018-06-20	criteria provided, single submitter	clinical testing	Loss-of-function variants in WWOX are known to be pathogenic (PMID: 25411445). This sequence change creates a premature translational stop signal (p.Glu195*) in the WWOX gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with WWOX-related disease. For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV000760719	SCV000890611	likely pathogenic	not provided	2018-09-12	criteria provided, single submitter	clinical testing	A variant that is likely pathogenic has been identified in the WWOX gene. The E195X nonsense variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The E195X variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The E195X variant is not observed in large population cohorts (Lek et al., 2016). Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.