Apart from Haemoglobin-S (HbS), there are other Hb variants (non-S sickling Hb variants) that cause sickle cell disease. However, the profiles of these non-S sickling Hb variants have neither been collated nor harmonised. Literature search in Pubmed (and other search engines) revealed 14 non-S sickling Hb variants viz: HbC-Harlem, HbC-Ziguinchor, HbS-Travis, HbS-Antilles, HbS-Providence, HbS-Oman, HbS-Cameroon, HbS-South End, Hb Jamaica Plain, HbC-Ndjamena, HbS-Clichy, HbS-San Martin, HbS-Wake and HbS-São Paulo. Generally, the non-S sickling Hb variants are double mutants that have the HbS mutation (GAG>GTG: βGlu6Val) and additional β-chain mutations. Consequently, non-S sickling Hb variants give positive solubility and sickling tests, but they differ from HbS with respect to stability, oxygen affinity and electro-chromatographic characteristics. Similarities and discrepancies between HbS and non-S sickling Hb variants create diagnostic pitfalls that can only be resolved by elaborate electro-chromatographic and/or genetic tests. It is therefore imperative that tropical haematologists should have thorough understanding of these atypical sickling Hb variants. Collated and harmonised appraisal of the non-S sickling Hb variants have not been previously under-taken. Hence, the aim of this paper is to provide comprehensive but concise historical, genetic, comparative, diagnostic and clinical overview of non-S sickling Hb variants. The elaborate techniques that are often required for precise diagnosis of non-S sickling Hb variants are regrettably not readily available in low resource tropical countries, which paradoxically carry the heaviest burden of sickling disorders. In order to avoid misdiagnosis of these atypical Hb mutants it is strongly recommended that tropical countries should upgrade their diagnostic laboratory facilities.

Apart from Haemoglobin-S (HbS), there are other Hb variants (non-S sickling Hb variants) that cause sickle cell disease. However, the profiles of these non-S sickling Hb variants have neither been collated nor harmonised. Literature search in Pubmed (and other search engines) revealed 14 non-S sickl...