Any hemoglobin that contains a mutation is a variant hemoglobin. A mutation can involve a delete of all or a portion of the gene leading to a reduced or absent production of globin proteins, or small changes in the DNA that affect the genes ability to function normally leading to the production of different types of hemoglobin. A mutation on chromosome 16 in the alpha globin gene can produce a different hemoglobin such as Constant Spring. However, mutations in this gene usually lead to the inactivation of the alpha globin protein production coded by the gene. A mutation can occur on chromosome 11, affecting one of the beta globins, leading to an abnormal hemoglobin. Beta globin gene mutations can lead to decreased production as well as inactivation of the gene. Not all of these mutations have been defined with DNA analysis, though many of them have and many are constantly being defined.

There are over 150 known mutations in the beta globin gene, producing beta thalassemia trait in the heterzygotic individual, and causing a variable degree of anemia in the homozygote. In addition, there are mutations such as that leading to hemoglobin E, which do not produce disease even in the homozygous state. However, hemoglobin E combined with other variant beta globins can produce mild to severe anemia. Many variant hemoglobins exist worldwide. Hemoglobins E and S are significant because they can be co-inherited with thalassemia trait to produce a disease that requires treatment. Hemoglobin E is very common among Southeast Asians; California Newborn Screening Program found that 1 in 12 Southeast Asians, and 1 in 4 Cambodian newborns had Hgb E trait. Hgb EE (homozygous) has not been shown to have serious medical implications. Hgb E-Beta thalassemia has a wide range of clinical manifestations, from mild anemia to significant anemia requiring chronic tranfusions.

Hemoglobin S (sickle cell) is prevalent among Africans and African Americans. Hgb S and beta thalassemia trait can be co-inherited to produce sickle beta zero (SB0) thalassemia. The clinical manifestations of this disease resemble Hgb SS disease.
 

Alpha Thalassemia - Beta Thalassemia - Variant Hemoglobin