ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.1371G>T (p.Arg457Ser) (rs113446173)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000488089 SCV000575393 uncertain significance not provided 2017-03-01 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000603890 SCV000711250 uncertain significance not specified 2016-06-20 criteria provided, single submitter clinical testing The p.Arg457Ser variant in WFS1 has been reported in one individual with atypica l Wolfram syndrome (Giuliano 2005). However, a variant affecting the remaining c opy of WFS1 was not identified in this individual, and a dominant family history of hearing loss was not described. This variant has been identified in 0.06% (3 9/66642) of European chromosomes by the Exome Aggregation Consortium (ExAC, http ://exac.broadinstitute.org; dbSNP rs113446173); however, its frequency is not hi gh enough to rule out a pathogenic role. Computational prediction tools and cons ervation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of this variant is uncertain.
Fulgent Genetics,Fulgent Genetics RCV000765780 SCV000897169 uncertain significance Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic deafness 6; Type 2 diabetes mellitus; Wolfram-like syndrome, autosomal dominant 2018-10-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001153150 SCV001314412 likely benign Autosomal dominant nonsyndromic deafness 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 Clinical Services Laboratory,Illumina RCV001153151 SCV001314413 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.
Personalized Diabetes Medicine Program,University of Maryland School of Medicine RCV001174421 SCV001337559 uncertain significance Monogenic diabetes 2018-12-07 criteria provided, single submitter research ACMG criteria: BS2 (87 heterozygotes in gnomAD- too many for dominant Wolfram-like syndrome);Identified in 46-year old male with symptoms of Wolfram (late-onset though), authors suspect additional variant was not able to be detected (PMID: 15605410) but don't think we can use this as evidence= VUS (REVEL 0.665 + PP3/5 predictors + BP4/4 predictors= conflicting evidence, not using)
Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit,IRCCS Fondazione Stella Maris RCV001640297 SCV001519277 likely pathogenic Spastic ataxia 2021-07-12 criteria provided, single submitter research
Department of Otolaryngology – Head & Neck Surgery,Cochlear Implant Center RCV001375054 SCV001571768 likely pathogenic Hearing impairment 2021-04-12 criteria provided, single submitter clinical testing PS1_Strong, PM2_Moderate, PM5_Moderate, PP3_Supporting
Gharavi Laboratory,Columbia University RCV000488089 SCV000920717 uncertain significance not provided 2018-09-16 no assertion criteria provided research
Clinical Genetics,Academic Medical Center RCV000488089 SCV001922369 uncertain significance not provided no assertion criteria provided clinical testing

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