ClinVar Miner

Submissions for variant NM_000558.5(HBA1):c.104T>G (p.Leu35Arg) (rs35203445)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985705 SCV001134177 uncertain significance not provided 2019-01-22 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001286162 SCV001472691 uncertain significance none provided 2019-12-12 criteria provided, single submitter clinical testing The Hb Queens variant (HBA1: c.104T>G; p.Leu35Arg, also known as Leu34Arg when numbered from the mature protein, rs35203445) has been reported heterozygously in multiple individuals with no associated clinical symptoms (Lee 1992, Lin 2013, HbVar database and references therein). However, it has been reported as mildly unstable (HbVar database and references therein), and its impact in the presence of pathogenic alpha globin variants is uncertain. This variant is reported in ClinVar (Variation ID: 15795). It is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The leucine at codon 35 is weakly conserved, and computational analyses (SIFT: Damaging, PolyPhen-2: Benign) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of this variant is uncertain at this time. REFERENCES Link to HbVar database for Hb Queens: http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=49 Lee N et al. A family case of beta-thalassemia minor and hemoglobin Queens: alpha 34 (B15) Leu-Arg. J Korean Med Sci. 1992; 7(4):385-8. Lin M et al. Molecular epidemiological survey of hemoglobinopathies in the Wuxi region of Jiangsu Province, eastern China. Hemoglobin. 2013; 37(5):454-66.
OMIM RCV000017133 SCV000037405 other HEMOGLOBIN OGI 2016-07-20 no assertion criteria provided literature only
OMIM RCV000017134 SCV000037406 other HEMOGLOBIN QUEENS 2016-07-20 no assertion criteria provided literature only

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