ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.79G>T (p.Glu27Ter) (rs33950507)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000507549 SCV000601319 pathogenic not provided 2017-06-30 criteria provided, single submitter clinical testing
Counsyl RCV000674991 SCV000800412 pathogenic beta Thalassemia 2018-06-04 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000507549 SCV000885563 pathogenic not provided 2018-03-09 criteria provided, single submitter clinical testing The HBB c.79G>T; Glu26Ter variant (rs33950507) has been identified in individuals with beta thalassemia that also harbored the HbE (HBB: Lys26Glu) variant (see link to HbVar, Fucharoen 1990). It is reported as pathogenic in ClinVar by one laboratory (Variation ID: 38650) and is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant induces an early termination codon and functional studies demonstrate an absence of beta globin protein (Neu-Yilik 2011). Based on the above information, this variant is considered pathogenic. References: Link to HbVar: Fucharoen G et al. Molecular basis of HbE-beta-thalassemia and the origin of HbE in northeast Thailand: identification of one novel mutation using amplified DNA from buffy coat specimens. Biochem Biophys Res Commun. 1990 Jul 31;170(2):698-704. Neu-Yilik G et al. Mechanism of escape from nonsense-mediated mRNA decay of human beta-globin transcripts with nonsense mutations in the first exon. RNA. 2011 May;17(5):843-54.
Integrated Genetics/Laboratory Corporation of America RCV000781460 SCV000919497 pathogenic Hemoglobinopathy 2017-12-14 criteria provided, single submitter clinical testing Variant summary: The HBB c.79G>T (p.Glu27X, also known as CD26 G>T) variant results in a premature termination codon, predicted to cause a truncated or absent HBB protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.85dupC/p.Leu29fsX16, c.110delC/p.Pro37fsX25, etc.). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 277088 control chromosomes. It has been reported in multiple affected individuals. Variant involving the same neucleotide c.79G>A/p.Glu27Lys is a common HbE variant and the region around codon 26 has been suggested as mutation hotspot(Fucharoen_1990). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
The ITHANET community portal, The Cyprus Institute of Neurology and Genetics RCV000674991 SCV001244658 pathogenic beta Thalassemia 2019-11-25 no assertion criteria provided curation

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