ClinVar Miner

Submissions for variant NM_002017.5(FLI1):c.1028A>G (p.Tyr343Cys)

dbSNP: rs1064797084
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002526993 SCV003441189 uncertain significance not provided 2022-04-15 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 343 of the FLI1 protein (p.Tyr343Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of FLI1-related conditions (PMID: 24100448). ClinVar contains an entry for this variant (Variation ID: 424633). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects FLI1 function (PMID: 24100448). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV002526993 SCV003923805 likely pathogenic not provided 2023-03-03 criteria provided, single submitter clinical testing Published functional studies suggest a damaging effect (luciferase assays revealed transcriptional activity of Y343C was significantly reduced compared to wildtype) (Stockley et al., 2013); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24100448, 27479822, 35021601)
OMIM RCV000487469 SCV000574548 pathogenic Bleeding disorder, platelet-type, 21 2017-04-25 no assertion criteria provided literature only
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology RCV000487469 SCV002515571 likely pathogenic Bleeding disorder, platelet-type, 21 no assertion criteria provided research

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.