Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003478079 | SCV000602286 | uncertain significance | not provided | 2024-07-26 | criteria provided, single submitter | clinical testing | The VWF c.1562_1563delinsCT (p.Cys521Ser) variant has not been reported in individuals with VWF-related conditions in the published literature. The frequency of this variant in the general population, 0.0045 (109/24426 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is deleterious or benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Johns Hopkins Genomics, |
RCV003320360 | SCV004024514 | uncertain significance | von Willebrand disease type 1 | 2023-06-22 | criteria provided, single submitter | clinical testing | This VWF missense variant (rs1555198442) has an entry in ClinVar (Variation ID: 439322), but has not been reported in the literature in individuals with VWF-related conditions. It has been identified in a large population dataset and the minor allele frequency is neither low enough to consider the variant rare (<0.1%) nor high enough to consider it a population polymorphism (>1%) within the African/African American subpopulation (gnomADv2.1.1: 109/24426 alleles; 0.4462 %, no homozygotes). Of two bioinformatics tools queried, one predicts that the substitution would be damaging, while one predicts that it would be tolerated. The cystine residue at this position is conserved across all species assessed except for one that has a serine at this position. We consider the clinical significance of VWF c.1562_1563delinsCT to be uncertain at this time. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003993990 | SCV004813678 | uncertain significance | not specified | 2024-02-22 | criteria provided, single submitter | clinical testing | Variant summary: VWF c.1562_1563delinsCT (p.Cys521Ser) results in a non-conservative amino acid change located in the von Willebrand factor, type D domain (IPR001846) of the encoded protein sequence. Two of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0002 in 1613320 control chromosomes in the gnomAD database, including 1 homozygotes. To our knowledge, no occurrence of c.1562_1563delinsCT in individuals affected with Von Willebrand Disease and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 439322). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Mayo Clinic Laboratories, |
RCV003478079 | SCV005408250 | uncertain significance | not provided | 2024-05-10 | criteria provided, single submitter | clinical testing |