When clinical consequences occur, they may include anemia due to hemolysis or polycythemia due to alterations in the oxygen affinity of the abnormal Hb. Common examples of hemoglobin variants associated with hemolysis include sickle Hb (Hb S) and Hb C. Hb variants can usually be detected by protein-based assay methods; however, DNA-based methods may be required for variants with ambiguous or unusual results from protein analysis.The major functional consequences of Hb structural variants can be classified as follows:
Change in physical properties (solubility): Common beta globin mutations can alter the solubility of the Hb molecule: Hb S polymerizes when deoxygenated and Hb C crystallizes. Reduced protein stability (instability): Unstable Hb variants are mutations that cause the Hb molecule to precipitate, spontaneously or upon oxidative stress, resulting in hemolytic anemia. Precipitated, denatured Hb can attach to the inner layer of the plasma membrane of the red blood cell (RBC) and form Heinz bodies. Change in oxygen affinity: High or low oxygen affinity Hb molecules are more likely than normal to adopt the relaxed (R, oxy) state or the tense (T, deoxy) state, respectively. High oxygen affinity variants (R state) cause polycythemia (e.g., Hb Chesapeake, Hb Montefiore). Low oxygen affinity variants can cause cyanosis (e.g., Hb Kansas, Hb Beth Israel). Oxidation of heme iron: Mutations of the heme binding site, particularly those affecting the conserved proximal or distal histidine residues, can produce M-hemoglobin, in which the iron atom in heme is oxidized from the ferrous (Fe2+) state to the ferric (Fe3+) state, with resultant methemoglobinemia.
Chemical abnormalities
Methemoglobinemia:
a condition caused by elevated levels of methemoglobin in the blood. Methaemoglobin is a form of Hb that contains the ferric [Fe3+] form of iron. The affinity for oxygen of ferric iron is impaired. The binding of oxygen to methaemoglobin results in an increased affinity for oxygen in the remaining heme sites that are in ferrous state within the same tetrameric haemoglobin unit. B)  Quantitative
Production abnormalities
Copy number variation (e.g., deletion, duplication, insertion) is also a common genetic cause of Hb disorders, and complex rearrangements and globin gene fusions can also occur. Thalassemias: Thalassemias are quantitative defects that lead to reduced levels of one type of globin chain, creating an imbalance in the ratio of alpha-like chains to beta-like chains. As noted above, this ratio is normally tightly regulated to prevent excess globin chains of one type from accumulating. The excess chains that fail to incorporate into Hb form non-functional aggregates that precipitate within the RBC. This can lead to premature RBC destruction in the bone marrow (beta thalassemia) and/or in the peripheral blood (alpha thalassemia). Types:
Alpha
Beta (Major)
Beta (Minor)

Hemoglobin variants
Haemoglobin variant are not necessarily pathological. For example, haemoglobin Valletta and haemoglobin Marseille are two haemoglobin variants which are non-pathological

HbS
HbC
HbE
Hb Barts
Hb D-Punjab
HbO (Hb O-Arab)
Hb G-Philadelphia
Hb H
Hb Constant Spring
Hb Hasharon
Hemoglobin Kenya
Hb Korle-Bu
Hb Lepore
Hb M
Hb Kansas
Hb J
Hb N-Baltimore
Hb Hope
Hb Pisa

Electrophoretic migration patterns
Hemoglobin variants can be detected by gel electrophoresis.