Submissions for variant NM_006005.3(WFS1):c.1692CCTCTT[1] (p.565LF[1])

dbSNP: rs797046113

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000194382	SCV000249461	likely pathogenic	Wolfram syndrome	2015-05-22	criteria provided, single submitter	clinical testing
GeneDx	RCV001762414	SCV002008634	likely pathogenic	not provided	2021-01-22	criteria provided, single submitter	clinical testing	In silico analysis supports a deleterious effect on protein structure/function; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In-frame deletion of 2 amino acids in a non-repeat region; This variant is associated with the following publications: (PMID: 20738327, 15605410, 23981289)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001824671	SCV002074344	pathogenic	Wolfram syndrome 1	2022-01-19	criteria provided, single submitter	clinical testing	Variant summary: WFS1 c.1698_1703delCCTCTT (p.Leu567_Phe568del) results in an in-frame deletion that is predicted to remove two amino acids from the encoded protein. The variant allele was found at a frequency of 4e-05 in 250888 control chromosomes (gnomAD). c.1698_1703delCCTCTT has been reported in the literature in individuals affected with Wolfram Syndrome 1 (examples: Astuti_2017 and Giuliano_2004). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001762414	SCV002163558	pathogenic	not provided	2024-11-28	criteria provided, single submitter	clinical testing	This variant, c.1698_1703del, results in the deletion of 2 amino acid(s) of the WFS1 protein (p.Leu567_Phe568del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs770916976, gnomAD 0.006%). This variant has been observed in individual(s) with autosomal recessive Wolfram syndrome (PMID: 10521293, 15605410, 23981289; internal data). This variant is also known as c.1689_1694delCTTCTT. ClinVar contains an entry for this variant (Variation ID: 212612). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV002503760	SCV002810885	likely pathogenic	Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome	2022-05-09	criteria provided, single submitter	clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV001824671	SCV003801419	likely pathogenic	Wolfram syndrome 1		criteria provided, single submitter	research	Potent mutations in WFS1 gene are associated with Wolfram's syndrome, an autosomal recessive condition, which cause diabetes mellitus, diabetes insipidus, deafness and optic atrophy. However no sufficient evidence is found to ascertain the role of this particular variant rs797046113 in Wolfram's syndrome yet.
PreventionGenetics, part of Exact Sciences	RCV004737305	SCV005359209	likely pathogenic	WFS1-related disorder	2024-06-02	no assertion criteria provided	clinical testing	The WFS1 c.1698_1703del6 variant is predicted to result in an in-frame deletion (p.Leu567_Phe568del). This variant has been reported in patients with autosomal recessive Wolfram syndrome in both homozygous and compound heterozygous states (Hardy et al. 1999. PubMed ID: 10521293; Giuliano et al. 2005. PubMed ID: 15605410; described as c.1689_1694delCTTCTT in Marshall et al. 2013. PubMed ID: 23981289; Internal Data, PreventionGenetics). This variant is reported in 0.0078% of alleles in individuals of European (non-Finnish) descent in gnomAD. This variant is interpreted as likely pathogenic.