ClinVar Miner

Submissions for variant NM_000552.5(VWF):c.4010C>T (p.Pro1337Leu)

dbSNP: rs61749400
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology RCV002222015 SCV002499572 likely pathogenic von Willebrand disease type 1 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000086718 SCV004221528 pathogenic not provided 2023-02-06 criteria provided, single submitter clinical testing The frequency of this variant in the general population, 0.000004 (1/250414 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in individuals with vWD Type 2B (PMIDs: 1373334 (1992), 9723578 (1998), 17155947 (2007), 26345337 (2015), 28436749 (2017), and 28971901 (2017)) and in individuals with unspecified vWD Type 2 (PMIDs: 17155947 (2007) and 33556167 (2021)). Family studies show that this variant segregates with vWD Type 2 or 2B (PMIDs: 1373334 (1992) and 17155947 (2007)). Inconclusive functional studies for this variant show enhanced ristocetin-induced platelet aggregation, normal or reduced ratios of ristocetin cofactor to vWF antigen, reduced collagen binding to vWF antigen ratio, and normal or reduced high molecular weight multimers (PMIDs: 17155947 (2007), 25185554 (2014), and 26345337 (2015)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, this variant is classified as pathogenic.
Academic Unit of Haematology, University of Sheffield RCV000086718 SCV000118923 not provided not provided no assertion provided not provided
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico RCV002243734 SCV002513377 uncertain significance von Willebrand disease type 2 2022-04-26 no assertion criteria provided clinical testing

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