ClinVar Miner

Submissions for variant NM_000558.3(HBA1):c.349G>A (p.Glu117Lys) (rs63749882)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001001805 SCV001159467 likely benign not specified 2018-12-21 criteria provided, single submitter clinical testing The HBA1 c.349G>A; Glu116Lys variant (rs63749882), also known as Hb O-Indonesia, is reported in the literature in the heterozygous state in individuals with no clinical symptoms (Chopra 2011, see link to HbVar). However, the phenotype of this variant in the presence of other alpha globin variants is unknown. This variant has been reported to have lower HbO levels than expected, suggesting protein instability; however, in vitro studies have shown the protein to be stable (Daud 2011, Molchanova 1994). This variant is only observed on two alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. The glutamic acid at codon 116 is weakly conserved, and computational analyses (SIFT: damaging, PolyPhen-2: benign) predict conflicting effects of this variant on protein structure/function, although these are low confidence predictions. Based on available information, this variant is considered to be likely benign. References: Link to HbVar for Hb O-Indonesia: Chopra A et al. Hemoglobin O (Indonesia) in India: a rare observation. Ann Hematol. 2011 90(3):353-4. Daud D et al. The hemoglobin O mutation in Indonesia: distribution and phenotypic expression. J Hum Genet. 2001 46(9):499-505. Molchanova TP et al. The differences in quantities of alpha 2- and alpha 1-globin gene variants in heterozygotes. Br J Haematol. 1994 88(2):300-6.
OMIM RCV000017127 SCV000037399 other HEMOGLOBIN O (INDONESIA) 2018-05-10 no assertion criteria provided literature only
OMIM RCV000017128 SCV000037400 other HEMOGLOBIN O (BUGINESE-X) 2018-05-10 no assertion criteria provided literature only
OMIM RCV000017129 SCV000037401 other HEMOGLOBIN BUGINESE-X 2018-05-10 no assertion criteria provided literature only
OMIM RCV000017130 SCV000037402 other HEMOGLOBIN O (OLIVIERE) 2018-05-10 no assertion criteria provided literature only
OMIM RCV000017131 SCV000037403 other HEMOGLOBIN OLIVIERE 2018-05-10 no assertion criteria provided literature only
Natera, Inc. RCV001275688 SCV001461048 likely benign alpha Thalassemia 2020-09-16 no assertion criteria provided clinical testing

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