ClinVar Miner

Submissions for variant NM_000553.4(WRN):c.1105C>T (p.Arg369Ter) (rs17847577)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000005782 SCV000285510 pathogenic Werner syndrome 2018-12-23 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg369*) in the WRN gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs17847577, ExAC 0.03%). This variant has been reported in many individuals affected with Werner syndrome (PMID: 8968742, 9225981, 25182132, 16786514). This variant is also known as 1336C>T and Arg368* in the literature. ClinVar contains an entry for this variant (Variation ID: 5449). Loss-of-function variants in WRN are known to be pathogenic (PMID: 16673358). For these reasons, this variant has been classified as Pathogenic.
Clinical Genomics Lab,St. Jude Children's Research Hospital RCV000722025 SCV000853200 likely pathogenic Medulloblastoma 2018-05-10 criteria provided, single submitter clinical testing This is a nonsene alteration in which a C is replaced by a T at coding nucleotide 1105 and is predicted to change an Arginine to a premature stop codon at amino acid codon 369. Classification criteria: PVS1, PM2
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000005782 SCV000967690 pathogenic Werner syndrome 2018-10-04 criteria provided, single submitter clinical testing The p.Arg369X variant in WRN has been reported in >20 homozygous or compound het erozygous individuals with Werner syndrome and has been reported to be the most common variant in Caucasian patients with Werner syndrome (Oshima 1996, Matsumot o 1997, Uhrhammer 2006, Huang 2006). This variant has been identified in 0.02% ( 52/276580) of chromosomes from the general population by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org/) and is reported in ClinVar (Variation ID: 5449). This nonsense variant leads to a premature termination cod on at position 369, which is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the WRN gene is an established disease mechani sm in individuals with Werner syndrome. In summary, this variant meets criteria to be classified as pathogenic for Werner syndrome in an autosomal recessive man ner based upon presence in affected individuals and predicted impact to the prot ein. ACMG/AMP Criteria applied: PVS1, PM3_VeryStrong.
OMIM RCV000005782 SCV000025964 pathogenic Werner syndrome 1997-07-01 no assertion criteria provided literature only
GeneReviews RCV000005782 SCV000055692 pathologic Werner syndrome 2011-11-17 no assertion criteria provided curation Converted during submission to Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.