A Practical Guide to Haemostasis

Prothrombin [F2] G20210A Mutation


The Prothrombin G20210A mutation arises from a single missense mutation [G→A] at position 20210 of the Prothrombin gene [F2]. The mutation affects the terminal 3' nucleotide of the 3' untranslated region (UTR) region of the Prothrombin mRNA, leading to elevated levels of Prothrombin in the plasma. Individuals who are heterozygous for the Prothrombin G20210A mutation have Prothrombin levels that are increased by approximately 30% and homozygous individuals by about 70%. Increased Prothrombin levels are associated with increased Thrombin generation and correlate with an increased risk of venous thromboembolic disease.

The Prothrombin G20210A mutation is a gain-of-function mutation, causing increased cleavage site recognition, increased 3' mRNA processing leading to an increase in mRNA accumulation within the cell and increased Prothrombin synthesis.

Principles & Method

A number of methods exist for the detection of the Prothrombin G20210A mutation. The majority of approaches depend on PCR to amplify genomic DNA followed by a number of methods to identify the presence or absence of the mutation. Such methods include the use of restriction enzymes which cleave the amplified DNA only if the mutation is present, DNA microarrays, real-time PCR, SSCP [Single Strand Conformation Polymorphism Analysis] but there are other approaches.


Most techniques can rapidly distinguish heterozygous individuals from homozygous mutant or wild type [i.e. normal]

Reference Ranges

There are no reference ranges for a genetic test - the mutation is either present in a heterozygous or homozygous form or it is not.