Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| NIHR Bioresource Rare Diseases, |
RCV000851644 | SCV000899684 | likely pathogenic | von Willebrand disease type 2 | 2019-02-01 | criteria provided, single submitter | research | |
| ISTH- |
RCV002222625 | SCV002500922 | likely pathogenic | von Willebrand disease type 1 | criteria provided, single submitter | clinical testing | ||
| Laboratory of Hematology, |
RCV000851644 | SCV002546284 | likely pathogenic | von Willebrand disease type 2 | 2020-12-10 | criteria provided, single submitter | research | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003317360 | SCV004020736 | uncertain significance | not specified | 2023-06-26 | criteria provided, single submitter | clinical testing | Variant summary: VWF c.3569G>A (p.Cys1190Tyr) results in a non-conservative amino acid change located in the trypsin inhibitor-like, cysteine rich domain (IPR002919) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251494 control chromosomes (gnomAD). c.3569G>A has been reported in the literature in the heterozygous state in individuals affected with or suspected of autosomal dominant Von Willebrand Disease (e.g. Schneppenheim_2010, Downes_2019, de Jong_2020). These data indicate that the variant may be associated with disease. Publications examining the functional impact of the variant in a heterozygous patient found that it resulted in an increased retention of unprocessed VWF in the ER compared to the WT protein, however it was not clear whether this effect was at a level sufficient to cause disease as although the patient had reduced high molecular weight VWF multimers in plasma, platelet multimers were found to be indistinguishable from healthy controls (de Jong_2020, Swinkels_2021). The following publications have been ascertained in the context of this evaluation (PMID: 31064749, 20351307, 32803740, 34532631). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and both classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| NIHR Bioresource Rare Diseases, |
RCV001003907 | SCV001161842 | likely pathogenic | Reduced von Willebrand factor activity | no assertion criteria provided | research |