Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002266293 | SCV002548092 | pathogenic | Hereditary von Willebrand disease | 2022-05-31 | criteria provided, single submitter | clinical testing | Variant summary: The variant identified by MLPA or other technology involves the deletion of exons 4-5 in the VWF gene. A presumed nomenclature of c.(220+1_221-1)_(532+1_533-1)del has been designated for the purposes of this classification. Although exact breakpoints of this deletion are not known, it is expected to result in a large in-frame deletion change in the VWF gene, a known mechanism of disease. The variant was absent in 21680 control chromosomes (gnomAD, Structural Variants dataset). Deletion of exons 4-5 has been reported in the literature in multiple individuals affected with Von Willebrand Disease (e.g. Sutherland_2009, Bowman_2013, Cartwright_2020). These data indicate that the variant is very likely to be associated with disease. Experimental evidence evaluating an impact on protein function demonstrated the variant results in markedly decreased secretion of VWF and interferes with the multimerization process (Sutherland_2009). Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, |
RCV001787157 | SCV001572626 | pathogenic | von Willebrand disease type 3 | 2021-04-12 | no assertion criteria provided | clinical testing | CNV Interpretation Scoring Rubric: Copy Number LOSS |