ClinVar Miner

Submissions for variant NM_000517.6(HBA2):c.242T>G (p.Leu81Arg)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001284977 SCV001471079 likely pathogenic none provided 2019-12-16 criteria provided, single submitter clinical testing The Hb Ann Arbor variant (HBA2: c.242T>G; p.Leu81Arg, also known as Leu80Arg when numbered from the mature protein rs281864863) is reported in the literature in two brothers affected with hemolytic microcytic anemia (Adams 1972, Adams 1974, HbVar database). Both affected brothers carried Hb Ann Arbor in the heterozygous state and were presumed to carry an additional undetermined alpha-thalassemia allele in trans, although this second allele was not determined (Adams 1974). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The affected brothers with Hb Ann Arbor exhibited 10-15% abnormal hemoglobin, while other family members that carried Hb Ann Arbor exhibited 2-5% abnormal hemoglobin (Adams 1974). The proportions of abnormal hemoglobin in heterozygous carriers, heat stability assays, and functional assays of protein synthesis all suggest Hb Ann Arbor is unstable and rapidly degraded (Adams 1972, Adams 1974). Based on available information, this variant is considered to be likely pathogenic. References: Link to Hb Ann Arbor in HbVar database: http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=123 Adams JG 3rd et al. Biosynthesis of hemoglobin Ann Arbor: evidence for catabolic and feedback regulation. Science. 1972 Jun 30;176(4042):1427-9. Adams JG 3rd. Hemoglobin Ann Arbor: disturbance in the coordinated biosynthesis of globin chains? Ann N Y Acad Sci. 1974 Nov 29;241(0):232-41.

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