Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000757362 | SCV000885555 | uncertain significance | not provided | 2022-10-06 | criteria provided, single submitter | clinical testing | The Hb E-Saskatoon variant (HBB: c.67G>A, p.Glu23Lys, also known as Glu22Lys when numbered from the mature protein, rs33959855, HbVar ID: 264) has been reported in a heterozygous state in individuals with no clinical symptoms (HbVar database and reference therein), and comprises half of the total hemoglobin (Birben 2001). Individuals carrying the variant in-trans to Hb S or a beta thalassemia pathogenic variant exhibit mild-moderate hematological abnormalities (Birben 2001, Couto 2014, Theodoridou 2003, HbVar database and references therein), while a homozygous individual presented only mild anemia (Birben 2001). The variant is listed in ClinVar (Variation ID: 15162), but is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. The at codon 23 is highly conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.536). Although Hb E-Saskatoon has not been associated with severe hematological symptoms, it has been associated with mild hematological changes in combination with other variants; overall, its clinical significance cannot be determined with certainty. References: Link to HbVar database: https://globin.bx.psu.edu/hbvar/menu.html Birben E et al. Homozygosity for Hb E-Saskatoon (beta22(B4)Glu-->Lys) in a Turkish patient. Hemoglobin. 2001; 25(4):409-15. PMID: 11791874. Couto GK et al. Association of hemoglobin E-Saskatoon with hemoglobin S: report of the first case found in Brazil. Acta Haematol. 2014;131(2):84-7. PMID: 24081202. Theodoridou S et al. The first case of a compound heterozygosity for Hb E-Saskatoon and HbS. Haematologica. 2003 Mar;88(3):ECR08. PMID: 12651286. |
| OMIM | RCV000016333 | SCV000036601 | other | HEMOGLOBIN E (SASKATOON) | 2019-11-14 | no assertion criteria provided | literature only |