Submissions for variant NM_006005.3(WFS1):c.1779G>C (p.Glu593Asp)

gnomAD frequency: 0.00063  dbSNP: rs144783536

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001705134	SCV000252491	likely benign	not provided	2021-01-11	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000196541	SCV000271193	likely benign	not specified	2016-02-07	criteria provided, single submitter	clinical testing	p.Glu593Asp in exon 8 of WFS1: This variant is not expected to have clinical si gnificance due to a lack of conservation across species, including mammals. Of n ote, 10 mammals have an aspartic acid (Asp) at this position despite high nearby amino acid conservation. In addition, computational prediction tools do not sug gest a high likelihood of impact to the protein. It has been identified in 0.2% (19/10398) of African chromosomes by the Exome Aggregation Consortium (ExAC, htt p://exac.broadinstitute.org; dbSNP rs144783536).
Eurofins Ntd Llc (ga)	RCV000196541	SCV000343653	likely benign	not specified	2016-08-17	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001705134	SCV002409277	benign	not provided	2023-11-27	criteria provided, single submitter	clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV003126582	SCV003801430	uncertain significance	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 rs144783536 in Wolfram's syndrome yet.
PreventionGenetics, part of Exact Sciences	RCV004541267	SCV004772310	likely benign	WFS1-related disorder	2022-05-20	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Ambry Genetics	RCV004020436	SCV004979914	likely benign	Inborn genetic diseases	2021-06-25	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Clinical Genetics, Academic Medical Center	RCV001705134	SCV002034439	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001705134	SCV002036975	likely benign	not provided		no assertion criteria provided	clinical testing