ClinVar Miner

Submissions for variant NM_000553.6(WRN):c.1165del (p.Arg389fs)

dbSNP: rs878854131
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000232269 SCV000285512 pathogenic Werner syndrome 2024-01-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg389Glufs*4) in the WRN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in WRN are known to be pathogenic (PMID: 16673358). This variant is present in population databases (rs558267186, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with Werner syndrome (PMID: 16786514). ClinVar contains an entry for this variant (Variation ID: 238117). For these reasons, this variant has been classified as Pathogenic.
Illumina Laboratory Services, Illumina RCV000232269 SCV000473321 likely pathogenic Werner syndrome 2018-04-23 criteria provided, single submitter clinical testing The WRN c.1165delA (p.Arg389GlufsTer4) variant results in a frameshift and is predicted to result in premature termination of the protein. The p.Arg389GlufsTer4 variant has been reported in at least one study in which it is identified in three unrelated individuals diagnosed with Werner syndrome, including two who carry the variant in a homozygous state and one who carries the variant in a compound heterozygous state (Uhrhammer et al. 2006). Control data are unavailable for this variant, which is reported at a frequency of 0.000195 in the South Asian population of the Genome Aggregation Database. Based on the clinical evidence and potential impact of frameshift variants, the p.Arg389GlufsTer4 variant is classified as likely pathogenic for Werner syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
CeGaT Center for Human Genetics Tuebingen RCV000999016 SCV001155398 likely pathogenic not provided 2016-11-01 criteria provided, single submitter clinical testing
Revvity Omics, Revvity Omics RCV000232269 SCV002020917 pathogenic Werner syndrome 2022-06-17 criteria provided, single submitter clinical testing
GeneDx RCV000999016 SCV002762262 pathogenic not provided 2022-12-08 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Observed with a second disease-causing variant in the WRN gene in patients with Werner syndrome in published literature (Oshima et al., 1996; Uhrhammer et al., 2006; Huang et al., 2006); This variant is associated with the following publications: (PMID: 9450180, 8968742, 34164337, 29641532, 9012406, 16786514, 16673358)
OMIM RCV000232269 SCV000025966 pathogenic Werner syndrome 1997-11-01 no assertion criteria provided literature only
Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals RCV000232269 SCV000574732 pathogenic Werner syndrome 2015-08-12 no assertion criteria provided clinical testing

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