Submissions for variant NM_006005.3(WFS1):c.568AAG[3] (p.Lys193del)

dbSNP: rs752461187

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota	RCV000761346	SCV000891332	likely pathogenic	Wolfram syndrome 1	2018-04-09	criteria provided, single submitter	clinical testing
GeneDx	RCV001561058	SCV001783585	likely pathogenic	not provided	2022-08-03	criteria provided, single submitter	clinical testing	In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25211237, 31589614)
Invitae	RCV001561058	SCV002174355	uncertain significance	not provided	2023-09-17	criteria provided, single submitter	clinical testing	This variant, c.577_579del, results in the deletion of 1 amino acid(s) of the WFS1 protein (p.Lys193del), but otherwise preserves the integrity of the reading frame. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 623222). This variant has been observed in individual(s) with Wolfram syndrome (PMID: 25211237). This variant is present in population databases (rs752461187, gnomAD 0.02%).
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV002252232	SCV002523916	likely pathogenic	See cases	2020-12-20	criteria provided, single submitter	clinical testing	ACMG classification criteria: PS4, PM2, PM3, PP1
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV000761346	SCV002773846	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 rs752461187 in Wolfram's syndrome yet.