ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.19GAG[1] (p.Glu8del) (rs63750928)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001289642 SCV001477607 likely pathogenic none provided 2019-11-25 criteria provided, single submitter clinical testing The Hb Leiden variant (HBB: c.22_24del; p.Glu8del, also known as Glu7del when numbered from the mature protein, rs63750928) is reported in the literature in multiple individuals affected with episodes of hemolytic anemia, although most exhibited normal hematology outside of hemolytic episodes (De Jong 1968, Rieder 1974, Schroeder 1982, HbVar database and references therein). Additionally, this variant has been observed in trans to HbE in a proband with a clinical picture of mild thalassemia intermedia and was absent from both parents, suggesting a de novo origin in this individual (Sanguansermsri 2003). The Hb Leiden variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant deletes a single glutamate residue, leaving the rest of the protein in-frame. Functional analyses suggest the variant is mildly unstable, although it is unclear if this is clinically significant (Rieder 1974). Still, based on available information, including its occurrence in multiple affected individuals, the Hb Leiden variant is considered to be likely pathogenic. References: HbVar link for Hb Leiden: http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=720 De Jong WW et al. Haemoglobin Leiden: deletion of beta-6 or 7 glutamic acid. Nature. 1968 Nov 23;220(5169):788-90. Rieder RF and James GW. Imbalance in alpha and beta globin synthesis associated with a hemoglobinopathy. J Clin Invest. 1974 Oct;54(4):948-56. Sanguansermsri P et al. Spontaneous mutation of the hemoglobin Leiden (beta 6 or 7 Glu-->0) in a Thai girl. Haematologica. 2003 Dec;88(12):ECR35. Schroeder WA et al. An unusual phenotypic expression of Hb-Leiden. Biochem Genet. 1982 Dec;20(11-12):1175-87.
OMIM RCV000016452 SCV000036720 other HEMOGLOBIN LEIDEN 2019-11-14 no assertion criteria provided literature only

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