Submissions for variant NM_000552.5(VWF):c.3943C>T (p.Arg1315Cys)

dbSNP: rs61749395

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000086712	SCV000602304	likely pathogenic	not provided	2023-06-26	criteria provided, single submitter	clinical testing	This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in affected individuals with VWD Type 1, 2A, 2M, or 3 (PMIDs: 34758185 (2022), 33556167 (2021), 30817071 (2019), 29984440 (2018), 28536718 (2017), 23355534 (2013), 21711445 (2011), 17190853 (2007), 11159522 (2001), 9723578 (1998), and 8088787 (1994)). Functional analysis of the variant showed decreased expression, abnormal folding, decrease of intermediate-molecular weight and high molecular weight multimers as well as a loss of function of vWF in the presence of either ristocetin or botrocetin (PMID: 11159522 (2001)). 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.
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000851600	SCV000899335	likely pathogenic	Hereditary von Willebrand disease	2019-02-01	criteria provided, single submitter	research
Laboratory of Hematology, Radboud University Medical Center	RCV002264655	SCV002546302	pathogenic	von Willebrand disease type 1	2020-12-10	criteria provided, single submitter	research
PreventionGenetics, part of Exact Sciences	RCV004549529	SCV004112926	likely pathogenic	VWF-related disorder	2023-08-01	criteria provided, single submitter	clinical testing	The VWF c.3943C>T variant is predicted to result in the amino acid substitution p.Arg1315Cys. This variant has been reported in individuals with Von Willebrand Disease (VWD) of types 1, 2A, 2M or 3 (Casaña et al. 1998. PubMed ID: 9723578; James et al. 2007. PubMed ID: 17190853; Starke et al. 2013. PubMed ID: 23355534; Liang et al. 2017. PubMed ID: 28536718; Elayaperumal et al. 2018. PubMed ID: 29984440; Freitas et al. 2019. PubMed ID: 30817071). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as likely pathogenic.
Academic Unit of Haematology, University of Sheffield	RCV000086712	SCV000118917	not provided	not provided		no assertion provided	not provided
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico	RCV002243732	SCV002513401	pathogenic	von Willebrand disease type 2	2022-04-26	no assertion criteria provided	clinical testing
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV000851600	SCV002515782	pathogenic	Hereditary von Willebrand disease		no assertion criteria provided	clinical testing