ClinVar Miner

Submissions for variant NM_000553.4(WRN):c.4148C>G (p.Ser1383Ter) (rs1060500080)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000463264 SCV000541487 uncertain significance Werner syndrome 2018-10-08 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal at codon 1383 (p.Ser1383*) within the last 15 codons in the penultimate exon of the WRN mRNA. While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated WRN protein. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a WRN-related disease. This variant is expected to result in the loss of the last 50 amino acids (residues 1383-1432) of the WRN protein. While a C-terminal nuclear localization signal (NLS, residues 1370-1375) is required for the correct cellular localization of the WRN protein (PMID: 9241267, 12244128, 11420665), it is not deleted by this truncation and functional studies have not been done to address the effect of this particular variant. In summary, this variant is a novel truncating variant with uncertain impact on protein function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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