Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular 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 | 2024-01-27 | 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. Loss-of-function variants in WRN are known to be pathogenic (PMID: 16673358). This variant is present in population databases (rs121908446, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with Werner syndrome (PMID: 8602509, 9012406). ClinVar contains an entry for this variant (Variation ID: 5444). RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (Invitae). For these reasons, this variant has been classified as Pathogenic. |
Institute Of Human Genetics Munich, |
RCV000005777 | SCV001150312 | pathogenic | Werner syndrome | 2019-07-03 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000005777 | SCV002814643 | pathogenic | Werner syndrome | 2022-05-25 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000005777 | SCV004208841 | pathogenic | Werner syndrome | 2023-07-20 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000005777 | SCV000025959 | pathogenic | Werner syndrome | 1996-04-12 | no assertion criteria provided | literature only |