ClinVar Miner

Submissions for variant NM_000518.4(HBB):c.194G>C (p.Gly65Ala) (rs33922018)

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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 RCV001287759 SCV001474479 uncertain significance none provided 2019-08-08 criteria provided, single submitter clinical testing The Hb Aubagne (HBB: c.194G>C; p.Gly65Ala, also known as Gly64Ala when numbered from the mature protein, rs33922018) variant is reported in the literature in the heterozygous state in a family with mild anemia and Heinz bodies and was considered mildly unstable (see link to HbVar; Lacan 2002). However, the effect when found with additional pathogenic HBB variants is unknown. Other variants at this codon (Hb J-Calabria, c.194G>A, p.Gly65Asp; Hb Calgary c.194G>T, p.Gly65Val; Hb Extremadura, c.[400G>C; 193G>A]; p.[Val134Leu; Gly65Ser]) have been reported in heterozygotes with mild anemia (Henderson 2016), and Hb J-Calabria has been reported with a second beta-thalassemia variant in an individual with chronic hemolytic anemia (see links to HbVar, Marinucci 1979). The Hb Aubagne variant is reported in ClinVar (Variation ID: 15599), and is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The glycine at codon 65 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, given the lack of clinical and functional data, the significance of the Hb Aubagne variant is uncertain at this time. References: Link to HbVar for Hb Aubagne: Link to HbVar for Hb J-Calabria: Henderson SJ et al. Ten Years of Routine alpha- and beta-Globin Gene Sequencing in UK Hemoglobinopathy Referrals Reveals 60 Novel Mutations. Hemoglobin. 2016;40(2):75-84. Lacan P et al. Hb aubagne [beta64(E8)Gly-Ala]: a new unstable beta chain variant found in a French family. Hemoglobin. 2002 May;26(2):163-7. Marinucci M et al. Studies on a family with Hb J Calabria (alpha 2 beta 2 64 (E8) Gly replaced by Asp). Hemoglobin. 1979;3(5):327-40.
OMIM RCV000016866 SCV000037136 other HEMOGLOBIN AUBAGNE 2017-12-12 no assertion criteria provided literature only

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