ClinVar Miner

Submissions for variant NM_000130.4(F5):c.1601G>A (p.Arg534Gln) (rs6025)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000616414 SCV000728219 benign not specified 2018-02-27 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Human Genome Sequencing Center Clinical Lab,Baylor College of Medicine RCV000205002 SCV000839955 pathogenic Factor V deficiency 2017-10-13 criteria provided, single submitter clinical testing This c.1601G>A (p.Arg534Gln) variant is known as the Factor V Leiden variant (legacy name p.Arg506Gln). Factor V Leiden variant is associated with thrombophilia due to activated protein C resistance [MIM:188055]. Studies suggest that the relative risk for venous thrombosis associated with the factor V Leiden variant in the absence of other acquired or environmental predispositions is approximately 4- to 7-fold for heterozygotes and 80-fold for homozygotes (PMID 16024978). This variant is classified as pathogenic. Homozygosity for this variant is also considered medically actionable.
Invitae RCV000205002 SCV000262346 pathogenic Factor V deficiency 2019-02-22 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 534 of the F5 protein (p.Arg534Gln). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and glutamine. This variant, also known as the Factor V Leiden mutation, is a well documented and common cause of activated protein C resistance (PMID: 8164741, 7910348). This variant has also been reported as R506Q. ClinVar contains an entry for this variant (Variation ID: 642). This variant disrupts the activated protein C cleavage site in the F5 protein and leads to a defective anticoagulant response in vitro (PMID: 7911872, 7910348). For these reasons, this variant has been classified as Pathogenic.
Knight Diagnostic Laboratories,Oregon Health and Sciences University RCV000454249 SCV000538025 pathogenic Thrombophilia due to activated protein C resistance 2016-03-30 criteria provided, single submitter clinical testing The c.1601G>A (p.Arg534Gln) missense variant is a common disease-causing variant in the F5 gene. This missense variant destroys one of three APC cleavage sites in factor V, rendering the protein resistant to APC inactivation. Arg534Gln heterozygotes and homozygotes have an increased risk for Factor V Thrombophilia; however, clinical expression is variable and most individuals never develop thrombosis (GeneReviews: Kujovich et al., 2010, http://www.ncbi.nlm.nih.gov/books/NBK1368/). Therefore, this collective evidence supports the classification of the c.1601G>A (p.Arg534Gln) as a Pathogenic variant for Factor V Thrombophilia.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000454249 SCV000271297 risk factor Thrombophilia due to activated protein C resistance 2016-01-07 criteria provided, single submitter clinical testing The p.Arg534Gln variant (previously known as p.Arg506Gln) in F5 is commonly referred to as "factor V Leiden" and has been associated with increased risk for venous thromboembolism (VTE) with an overall odds ratio (OR) of 4.3 (Simone 2013). The frequency of this variant varies by population, with the highest heterozygosity rate found in Europe. It has been identified in 3.1% (2085/66714) of European chromosomes and 0.4% (46/10404) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs6025). The factor V Leiden variant is present in approximately 15-20% of individuals with a first deep vein thrombosis (DVT) and in up to 50% of individual with recurrent VTE or an estrogen-related thrombosis. Many individuals with the factor V Leiden allele never develop thrombosis, however, evidence suggests that the relative risk for VTE is increased 3- to 8-fold in factor V Leiden heterozygotes and 10- to 80-fold in homozygotes. Lastly, heterozygosity for factor V Leiden is associated with a 2- to 3-fold increase in relative risk for pregnancy loss, and possibly other pregnancy complications such as preeclampsia, fetal growth retardation, and placental abruption.
OMIM RCV000000674 SCV000020824 pathogenic Thrombophilia due to factor V Leiden 2006-06-15 no assertion criteria provided literature only
OMIM RCV000000675 SCV000020825 risk factor Ischemic stroke, susceptibility to 2006-06-15 no assertion criteria provided literature only
OMIM RCV000000676 SCV000020826 risk factor Budd-Chiari syndrome, susceptibility to 2006-06-15 no assertion criteria provided literature only
OMIM RCV000023935 SCV000045226 risk factor Recurrent abortion 2006-06-15 no assertion criteria provided literature only

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