ClinVar Miner

Submissions for variant NM_000553.6(WRN):c.3913C>T (p.Arg1305Ter) (rs121908446)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000005777 SCV000712113 pathogenic Werner syndrome 2016-05-16 criteria provided, single submitter clinical testing The p.Arg1305X variant in WRN has been reported in at least 5 homozygous patient s with Werner syndrome (Yu 1997). It has also been identified in 1/121,072 chrom osomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org ; dbSNP rs121908446). This nonsense variant leads to a premature termination cod on at position 1305, which is predicted to lead to a truncated or absent protein . Biallelic loss of function of the WRN gene is associated with Werner syndrome. In summary, the p.Arg1305X variant meets our criteria to be classified as patho genic for Werner syndrome in an autosomal recessive manner based upon its predic ted functional impact, identification in patients and low frequency in controls.
Invitae RCV000005777 SCV000817846 pathogenic Werner syndrome 2019-12-23 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1305*) in the WRN gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs121908446, ExAC 0.009%). This variant has been reported as homozygous in several individuals affected with Werner syndrome (PMID: 8602509, 9012406). ClinVar contains an entry for this variant (Variation ID: 5444). Loss-of-function variants in WRN are known to be pathogenic (PMID: 16673358). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000005777 SCV000025959 pathogenic Werner syndrome 1996-04-12 no assertion criteria provided literature only
Institute of Human Genetics, Klinikum rechts der Isar RCV000005777 SCV001150312 pathogenic Werner syndrome 2019-07-03 no assertion criteria provided clinical testing

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