General Information About Factor V Leiden
Other Names for Factor V Leiden
- Factor V Leiden
- Factor V Leiden (RQ506Q)
- Factor V Leiden (G1691A) Mutation
- Factor V Variant
- Factor V G1691A
- Factor V R506Q
- Factor V Leiden (F5) R506Q Variant
- Factor V Leiden thrombophilia
- FVL Mutation
- FVL 1691G >A mutation
- F5 R506Q
- Resistance to Activated Protein C
- Resistance to APC
- Activated Protein C Resistance
- APC Resistance
- APC resistance, Leiden type
- rs6025 SNP
- Hereditary resistance to activated protein C
Factor V Leiden Genetics
Variant – Factor V (F5) c.1601G>A; p.Arg534Gln. Legacy nomenclature R506Q (1691G>A).
Inheritance – Semidominant; both heterozygotes and homozygotes are at increased risk for VTE.
Penetrance – Lifetime risk of VTE is 10 percent for heterozygotes and 80 percent for homozygotes.
Factor V Leiden is an autosomal dominant genetic condition which exhibits incomplete penetrance, meaning that not every person who has the mutation will develop the disease.
Test Interpretation – Sensitivity/Specificity – Analytical sensitivity/specificity: 99.9%
Factor V Leiden Genetic rs6025 SNP
Single Nucleotide Polymorphism (SNP; pronounced snip): A precise position along a chromosome where the DNA of different people may vary. Generally two alternate alleles are found at a particular SNP. The 1000 Genomes Project reported 84.7 million SNPs in the human genome (Nature, October 2015). The SNPs that have medical or health consequences for you and your loved ones are the focus of SNPedia.
rs6025 represents a SNP in the Factor V F5 gene, encoding a change in the protein from an arginine at position 506 to a glutamine. The resulting rs6025(A) allele encodes a mutation known as the Leiden mutation, R506Q. This mutation is often referred to as the G1691A or 1691G-A change.
Click on the link below for more information.
The Pathophysiology of Factor V Leiden
The genetic variation or polymorphism (G1691A or R506Q) is from a single nucleotide substitution at position 1691 where a guanine (G) is substituted for an adenine (A). This type of nucleotide substitution results in a missense mutation.
This single change in the nucleotide sequence (or missense mutation) causes a change in the amino acid placed at position 506 on the protein molecule; the amino acid changes from an arginine (R; Arg) to a glutamine (Q; Gln), thus the reason the polymorphism is identified as R506Q. This single change in an amino acid can alter the activity and binding characteristics of factor V because at normal pH (7.35-7.45), Gln is not charged however Arg is positively charged.
In fact, this is one of the sites where activated protein C cleaves factor V to inactivate it, but now it can’t because of this change. Thus, the mutated protein structure of factor V is now less responsive to the inhibitory action of activated protein C. This allows factor V to continue to be available for use in the propagation and formation of a clot.
The FV gene is located on the long arm (q arm) of chromosome 1 at position 23. This mutation results of a single change in one amino acid (single nucleotide polymorphism; SNP) in the factor V protein. Specifically an arginine is replaced by a glutamine at protein position 506 (Arg506Gln or R506Q).