Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000506527 | SCV005878006 | pathogenic | not provided | 2024-04-02 | criteria provided, single submitter | clinical testing | The HBB c.184A>T; p.Lys62Ter variant (also known as Codon 61 (A->T), rs33995148, HbVar ID: 866, ClinVar Variation ID: 15407) is reported in the literature in an individual affected with beta-thalassemia major that carried a second beta(0) allele in trans (Gonzalez-Redondo 1988). This variant is also absent from the Genome Aggregation Database (v2.1.1), indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Link to HbVar database: https://globin.bx.psu.edu/hbvar/menu.html Gonzalez-Redondo JM et al. Clinical and genetic heterogeneity in black patients with homozygous beta-thalassemia from the southeastern United States. Blood. 1988 Sep;72(3):1007-14. PMID: 2458145. |
| Fulgent Genetics, |
RCV002504795 | SCV002816612 | pathogenic | Dominant beta-thalassemia; Heinz body anemia; Hb SS disease; alpha Thalassemia; Malaria, susceptibility to; METHEMOGLOBINEMIA, BETA TYPE; Erythrocytosis, familial, 6; Hereditary persistence of fetal hemoglobin; Beta-thalassemia HBB/LCRB | 2022-01-26 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV001078254 | SCV002089214 | pathogenic | beta Thalassemia | 2025-08-15 | criteria provided, single submitter | clinical testing | The c.184A>T variant in HBB is a nonsense variant predicted to introduce a stop codon at amino acid 62. This variant is expected to result in nonsense mediated decay, truncation, or a dysfunctional protein product. This variant is rare in the general population with a frequency below the threshold expected for the associated phenotype(s). This variant has been observed in one or more individuals affected with the associated recessive disease, as either homozygous or compound heterozygous with a second variant (PMID: 2458145). Given the available evidence, this variant is classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001078254 | SCV001338370 | pathogenic | beta Thalassemia | 2020-02-17 | criteria provided, single submitter | clinical testing | Variant summary: HBB c.184A>T (p.Lys62X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the 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. The variant was absent in 251424 control chromosomes. c.184A>T has been reported in the literature as an African American variant originally identified in one individual affected with severe transfusion dependent Beta Thalassemia (Gonzalez-Redondo_1988). It has subsequently been cited in the literature and locus specific databases. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic citing the original literature report. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000506527 | SCV000601255 | pathogenic | not provided | 2023-03-09 | criteria provided, single submitter | clinical testing | This nonsense variant causes the premature termination of HBB protein synthesis. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in a child affected with beta thalassemia major (PMID: 2458145 (1988)). Based on the available information, this variant is classified as pathogenic. |
| The ITHANET community portal, |
RCV001078254 | SCV001244397 | pathogenic | beta Thalassemia | 2019-11-25 | no assertion criteria provided | curation | |
| OMIM | RCV000016661 | SCV000036930 | pathogenic | Beta zero thalassemia | 1988-09-01 | no assertion criteria provided | literature only |