Submissions for variant NM_006005.3(WFS1):c.1495C>T (p.Leu499Phe)

gnomAD frequency: 0.00810  dbSNP: rs114152068

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038640	SCV000062318	benign	not specified	2012-05-07	criteria provided, single submitter	clinical testing	Leu499Phe in Exon 08 of WFS1: This variant is not expected to have clinical sign ificance because it has been identified in 2.6% (98/3738) of African American ch romosomes from a broad population by the NHLBI Exome Sequencing Project (http:// evs.gs.washington.edu/EVS; dbSNP rs114152068).
GeneDx	RCV000038640	SCV000252485	benign	not specified	2014-06-23	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Eurofins Ntd Llc (ga)	RCV000038640	SCV000341004	benign	not specified	2016-05-26	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000329452	SCV000450618	likely benign	WFS1-Related Spectrum Disorders	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000384013	SCV000450619	likely benign	Autosomal dominant nonsyndromic hearing loss 6	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Personalized Diabetes Medicine Program, University of Maryland School of Medicine	RCV000664089	SCV000787541	benign	Monogenic diabetes	2019-01-11	criteria provided, single submitter	research	ACMG criteria: BA1 (2.5% in gnomAD Africans), BS2 (equal cases and controls in T2DM and 3 homozygotes in gnomAD) (REVEL 0.229 + PP3/3 predictors + BP4/6 predictors= conflicting evidence, not using)=benign
Labcorp Genetics (formerly Invitae), Labcorp	RCV000870509	SCV001012010	benign	not provided	2025-02-04	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000870509	SCV002506003	benign	not provided	2023-11-22	criteria provided, single submitter	clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002464097	SCV002640380	likely benign	Wolfram syndrome 1		criteria provided, single submitter	research	Mutations in WFS1 gene are associated with Wolfram's syndrome, an autosomal recessive condition, which cause diabetes mellitus, diabetes insipidus, deafness and optic atrophy. rs114152068 variant is also seen in patients with Diabetes Mellitus. However, the role of this particular variant is yet to be ascertained.
Fulgent Genetics, Fulgent Genetics	RCV002504898	SCV002809028	likely benign	Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome	2021-11-10	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000870509	SCV004147637	benign	not provided	2023-02-01	criteria provided, single submitter	clinical testing	WFS1: BP4, BS1, BS2
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV004814957	SCV005073638	uncertain significance	Optic atrophy	2021-01-01	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000870509	SCV005257166	likely benign	not provided		criteria provided, single submitter	not provided
Clinical Genetics, Academic Medical Center	RCV000038640	SCV001919081	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000038640	SCV001964489	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000870509	SCV002036921	likely benign	not provided		no assertion criteria provided	clinical testing