Submissions for variant NM_000552.5(VWF):c.4309G>A (p.Ala1437Thr)

gnomAD frequency: 0.00001  dbSNP: rs61750084

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000086752	SCV000602315	likely pathogenic	not provided	2024-05-10	criteria provided, single submitter	clinical testing	The VWF c.4309G>A (p.Ala1437Thr) variant has been reported in the published literature in individuals with Type 2 von Willebrand disease (VWD) (PMIDs: 25185554 (2014), 22315491 (2012), 19506361 (2009), 11325649 (2001)). Experimental studies report conflicting evidence that this variant impacts proper gene function (PMIDs: 27889474 (2016), 25185554 (2014)). In one family, the variant shows strong segregation with disease in multiple family members affected by VWD (PMID: 11325649 (2001)). The frequency of this variant in the general population, 0.000008 (2/251128 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is consistent with pathogenicity. 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 likely pathogenic.
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV002243741	SCV004013127	likely pathogenic	von Willebrand disease type 2		criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV004760373	SCV005368308	likely pathogenic	von Willebrand disease type 1	2024-06-18	criteria provided, single submitter	clinical testing	Criteria applied: PS4_MOD,PS3_SUP,PM1_SUP,PP1,PP3
Mayo Clinic Laboratories, Mayo Clinic	RCV000086752	SCV005414036	likely pathogenic	not provided	2024-02-19	criteria provided, single submitter	clinical testing	PP1_moderate, PP3, PP5, PM2_moderate, PS3_supporting, PS4_moderate
Academic Unit of Haematology, University of Sheffield	RCV000086752	SCV000118958	not provided	not provided		no assertion provided	not provided
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico	RCV002243741	SCV002513395	uncertain significance	von Willebrand disease type 2	2022-04-26	no assertion criteria provided	clinical testing