ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.435G>C (p.Lys145Asn) (rs35020585)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001000142 SCV001156626 pathogenic not specified 2019-01-27 criteria provided, single submitter clinical testing The Hb Andrew-Minneapolis variant (HBB: c.435G>C; p.Lys145Asn, also known as Lys144Asn when numbered from the mature protein) (rs35020585) is reported in the literature in multiple individuals with familial erythrocytosis, in both the heterozygous and homozygous states (Gomi 1992, Mehta 2017, Ropero 2013, Zak 1974, HbVar and references therein). In one case, this variant was reported to occur de novo, in trans to a large deletion, in an individual with marked erythrocytosis (Ropero 2013). This variant is present on a single chromosome in the Genome Aggregation Database, indicating it is not a common polymorphism. The lysine at codon 145 is highly conserved, computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious, and functional studies demonstrate increased oxygen affinity of the variant protein (Zak 1974, HbVar and references therein). Based on available information, this variant is considered to be pathogenic. References: Link to HbVar for Hb Andrew-Minneapolis: http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=567 Gomi T et al. Hemoglobin Andrew-Minneapolis (beta 144 (HCl) lysine----asparagine) in a Japanese family. Intern Med. 1992 May;31(5):659-61. Mehta P et al. Identification of high oxygen affinity hemoglobin (Hb Andrew-Minneapolis) in an Indian family. Int J Lab Hematol. 2017 Apr;39(2):e51-e54. Ropero P et al. Erythrocytosis in a child due to Hb Andrew-Minneapolis [beta-144(HC1)Lys?Asn (AAG>AAT or AAC)] associated with a Spanish (dbeta)(0)-thalassemia. Hemoglobin. 2013;37(1):48-55. Zak SJ et al. Hemoglobin Andrew-Minneapolis alpha 2 A beta 2 144 Lys leads to Asn: a new high-oxygen-affinity mutant human hemoglobin. Blood. 1974 Oct;44(4):543-9.
OMIM RCV000016249 SCV000036517 other HEMOGLOBIN ANDREW-MINNEAPOLIS 2017-12-12 no assertion criteria provided literature only
OMIM RCV000641406 SCV000763047 pathogenic Erythrocytosis 6, familial 1978-09-01 no assertion criteria provided literature only

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