Submissions for variant NM_006005.3(WFS1):c.1096C>T (p.Gln366Ter)

gnomAD frequency: 0.00001  dbSNP: rs761320763

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV001310826	SCV001500778	pathogenic	not provided	2020-07-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002499595	SCV002810262	likely pathogenic	Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome	2022-02-16	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001310826	SCV003288805	pathogenic	not provided	2022-09-01	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: 1012716). This premature translational stop signal has been observed in individual(s) with autosomal recessive Wolfram syndrome (PMID: 9817917, 17568405, 21602428, 28432734). This variant has been reported in individual(s) with autosomal dominant Wolfram-like syndrome (PMID: 9817917); however, the role of the variant in this condition is currently unclear. This variant is present in population databases (rs761320763, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Gln366*) in the WFS1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 525 amino acid(s) of the WFS1 protein.
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001310826	SCV001807650	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001310826	SCV001952445	pathogenic	not provided		no assertion criteria provided	clinical testing