Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
NIHR Bioresource Rare Diseases, |
RCV000851803 | SCV000899771 | likely pathogenic | Hereditary von Willebrand disease | 2019-02-01 | criteria provided, single submitter | research | |
ARUP Laboratories, |
RCV001811479 | SCV002050233 | pathogenic | not provided | 2020-11-23 | criteria provided, single submitter | clinical testing | The VWF c.4931G>A; p.Trp1644Ter variant (rs1591862022) is reported in the literature in a homozygous individual affected with a coagulation disorder (Downes 2019). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. VWF loss-of-function is an established mechanism of disease, and truncating variants downstream of p.Trp1644Ter have been reported in individuals affected with type 3 von Willebrand disease and are considered disease-causing (Kasatkar 2014). Based on available information, the p.Trp1644Ter variant is considered to be pathogenic. References: Downes K et al. Diagnostic high-throughput sequencing of 2396 patients with bleeding, thrombotic, and platelet disorders. Blood. 2019 Dec 5;134(23):2082-2091. Kasatkar P, Shetty S, Ghosh K. Genetic heterogeneity in a large cohort of Indian type 3 von Willebrand disease patients. PLoS One. 2014 Mar 27;9(3):e92575. |