Submissions for variant NM_000173.7(GP1BA):c.380G>A (p.Arg127Gln)

gnomAD frequency: 0.00004  dbSNP: rs749454966

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003388106	SCV004099934	uncertain significance	not specified	2023-09-18	criteria provided, single submitter	clinical testing	Variant summary: GP1BA c.380G>A (p.Arg127Gln) results in a conservative amino acid change located in the Leucine-rich repeat (IPR001611) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.9e-05 in 280606 control chromosomes (gnomAD). c.380G>A has been reported in the literature in at least one individual affected with Platelet-Type von Willebrand Disease (Bury_2022). These data do not allow any conclusion about variant significance. Experimental evidence using transfected CHO cells show the variant protein has increased affinity for VWF, indicating a gain-in-function, which is one possible mechanism of disease (OMIM 606672). The following publication have been ascertained in the context of this evaluation (PMID: 34619770). One ClinVar submitter has assessed the variant since 2014, and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV002245368	SCV002515576	likely pathogenic	Pseudo von Willebrand disease		no assertion criteria provided	clinical testing