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

dbSNP: rs878854131

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000232269	SCV000285512	pathogenic	Werner syndrome	2024-09-30	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	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)
Fulgent Genetics, Fulgent Genetics	RCV000232269	SCV005676835	pathogenic	Werner syndrome	2024-03-30	criteria provided, single submitter	clinical testing
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