ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.205C>T (p.Leu69Phe) (rs33961459)

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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 RCV001286462 SCV001473037 pathogenic none provided 2019-12-12 criteria provided, single submitter clinical testing The Hb Loves Park variant (HBB: c.205C>T; p.Leu69Phe, also known as Leu68Phe when numbered from the mature protein, rs33961459) is reported in the literature in the heterozygous state in multiple individuals affected with microcytic anemia (Ferreira 2006, HbVar database and references therein). In one instance, this variant was observed in an affected proband but was not found in either parent despite demonstrated parentage, indicating a de novo origin (Ferreira 2006). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The leucine at codon 69 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Additionally, another amino acid substitution at this codon (p.Leu69Pro, also known as Hb Mizuho) has been reported de novo in multiple individuals with hemolytic anemia and is considered disease-causing (HbVar database and references therein). Based on available information, the Hb Loves Park variant is considered to be pathogenic. References: Link to Hb Loves Park in HbVar: http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=375 Link to Hb Mizuho in HbVar: http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=373 Ferreira C et al. Hemoglobin Loves Park [beta68 (E12) Leu-->Phe]: report of five cases including one originating from a de novo mutation. Am J Hematol. 2006 Apr;81(4):256-61.
OMIM RCV000016880 SCV000037150 other HEMOGLOBIN ROCKFORD 2017-12-12 no assertion criteria provided literature only

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