Submissions for variant NM_006005.3(WFS1):c.1294C>G (p.Leu432Val)

dbSNP: rs35031397

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000155411	SCV000169819	benign	not specified	2014-03-28	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000155411	SCV000205098	benign	not specified	2014-09-26	criteria provided, single submitter	clinical testing	Leu432Val in exon 08 of WFS1: This variant is not expected to have clinical sign ificance because it has been identified in 0.5% (43/8600) of European American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS; dbSNP rs35031397).
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000155411	SCV000297197	likely benign	not specified	2015-11-10	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000351887	SCV000450607	likely benign	WFS1-Related Spectrum Disorders	2018-03-06	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
CeGaT Center for Human Genetics Tuebingen	RCV000415767	SCV000493152	likely benign	not provided	2025-02-01	criteria provided, single submitter	clinical testing	WFS1: PM5, BS2
Personalized Diabetes Medicine Program, University of Maryland School of Medicine	RCV000445544	SCV000537010	uncertain significance	Monogenic diabetes	2016-07-22	criteria provided, single submitter	research	ACMG Criteria:PP3, BP6 (ClinVar with 2 submitters calling this variant benign/Partners and GeneDx) Notes: no statistical difference between [deafness and DM] and 49 controls with this variant in Domenech et al 2002 EJHG (PMID:12107816).
Eurofins Ntd Llc (ga)	RCV000155411	SCV000705650	benign	not specified	2017-03-09	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000415767	SCV000884909	benign	not provided	2023-10-26	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000415767	SCV001013096	likely benign	not provided	2025-02-03	criteria provided, single submitter	clinical testing
Mendelics	RCV000987408	SCV001136697	likely benign	Wolfram syndrome 1	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001157342	SCV001318904	benign	Autosomal dominant nonsyndromic hearing loss 6	2018-03-06	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Athena Diagnostics	RCV000155411	SCV001477209	benign	not specified	2019-12-06	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000155411	SCV002064897	benign	not specified	2019-07-10	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000155411	SCV001920114	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000415767	SCV001972288	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000415767	SCV002036058	likely benign	not provided		no assertion criteria provided	clinical testing
Center for Computational Biology & Bioinformatics, University of California, San Diego	RCV004567069	SCV005049975	uncertain significance	Meniere disease	2024-06-03	no assertion criteria provided	research