ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.577A>C (p.Lys193Gln)

gnomAD frequency: 0.00249  dbSNP: rs41264699
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Total submissions: 17
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000155410 SCV000205097 benign not specified 2013-08-30 criteria provided, single submitter clinical testing p.Lys193Gln in exon 5 of WFS1: This variant is not expected to have clinical sig nificance because it has been identified in 0.4% (30/7020) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs41264699).
Preventiongenetics, part of Exact Sciences RCV000155410 SCV000311336 benign not specified criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000333986 SCV000450575 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.
Illumina Laboratory Services, Illumina RCV000386661 SCV000450576 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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics RCV000433970 SCV000510960 likely benign not provided 2016-07-22 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
Personalized Diabetes Medicine Program, University of Maryland School of Medicine RCV000445506 SCV000537004 benign Monogenic diabetes 2018-11-21 criteria provided, single submitter research ACMG criteria: BS1 (1.3% in gnomAD S Asian, 1% gnomAD AJ), BS2 (74 cases and 62 control in T2DM and 5 homozygotes in gnomAD)=benign (REVEL 0.223 + PP3/5 predictors + BP4/4 predictors: conflicting evidence, not using)
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000433970 SCV000605609 benign not provided 2023-11-11 criteria provided, single submitter clinical testing
Invitae RCV000433970 SCV001005755 benign not provided 2024-01-29 criteria provided, single submitter clinical testing
Broad Institute Rare Disease Group, Broad Institute RCV000333986 SCV001435176 benign Autosomal dominant nonsyndromic hearing loss 6 criteria provided, single submitter research The heterozygous p.Lys193Gln variant in WFS1 has been identified in an individual with sensorineural hearing loss and in the compound heterozygous state in an individual with gait instability, optic atrophy, and cerebellar dysarthria (PMID: 12073007, 25497598), and has been identified in >1% of South Asian chromosomes and 4 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as benign for autosomal dominant sensorineural hearing loss.
Genetic Services Laboratory, University of Chicago RCV000155410 SCV002064894 likely benign not specified 2021-08-31 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000433970 SCV002544861 benign not provided 2023-08-01 criteria provided, single submitter clinical testing WFS1: BS1, BS2
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002464131 SCV002605560 likely risk allele Wolfram syndrome 1 2024-02-21 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. rs41264699 variant is also seen in patients with Diabetes Mellitus. However, the role of this particular variant is yet to be ascertained. This variant is found to be a potent moderate impact, deleterious variant with a CADD score of 24 and sufficient scientific evidence to support the reported classification. This is found more frequently in Wolfram syndrome cases as per recent evidence as well.
Fulgent Genetics, Fulgent Genetics RCV002498754 SCV002809032 benign Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2022-05-05 criteria provided, single submitter clinical testing
Clinical Genetics, Academic Medical Center RCV000155410 SCV001920951 benign not specified no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000433970 SCV001955777 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000433970 SCV001966979 likely benign not provided no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000433970 SCV002036871 likely benign not provided no assertion criteria provided clinical testing

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