ClinVar Miner

Submissions for variant NM_000552.5(VWF):c.3971G>C (p.Gly1324Ala)

dbSNP: rs61749399
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen von Willebrand Disease Variant Curation Expert Panel, ClinGen RCV004821269 SCV005442540 pathogenic von Willebrand disease type 2M 2024-08-13 reviewed by expert panel curation The NM_000552.5(VWF):c.3971G>C (p.Gly1324Ala) missense variant has been reported in at least one type 2M patient with VWF:RCo/VWF:Ag ratio of 0.44 (PMID: 12008946; PS4_supporting). The variant segregated with VWD type 2M through 3 affected meioses from this family (PP1; PMID:12008946). Another missense variant in the same codon has been reported in a patient with VWD type 2 Gly1324Ser, which has been classified likely pathogenic by the ClinGen VWD VCEP (PM5). The computational predictor REVEL gives a score of 0.719, which is above the ClinGen VWD VCEP threshold of >0.644 and predicts a damaging effect on VWF function (PP3). Platelet/GP1b binding assays performed with the Gly1324Ala recombinant mutant vWF expressed by COS-7 showed no binding indicating that this variant has a damaging effect on protein function (PMIDs: 12008946, 10845912; PS3). This variant is absent from gnomAD v4.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as Pathogenic for autosomal dominant VWD type 2M based on the ACMG/AMP criteria applied, as specified by the ClinGen VWD VCEP: PS3, PM2_supporting, PM5, PP1, PP3, PS4_supporting.
Academic Unit of Haematology, University of Sheffield RCV000086717 SCV000118922 not provided not provided no assertion provided not provided

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.