ClinVar Miner

Submissions for variant NM_000553.6(WRN):c.3383+1G>T (rs1413656527)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000798163 SCV000937764 pathogenic Werner syndrome 2019-06-07 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 28 of the WRN gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with Werner syndrome who also carried another pathogenic variant in the WRN gene (PMID: 8968742). This variant is also referred to as a deletion of nucleotides 3541-3614 in the literature. Experimental studies have shown that this variant results in skipping of exon 28 which leads to a frameshift and truncated protein product (PMID: 8968742 16673358). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in WRN are known to be pathogenic (PMID: 16673358). For these reasons, this variant has been classified as Pathogenic.

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