Total submissions: 9
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Natera, |
RCV000590298 | SCV007536068 | pathogenic | beta Thalassemia | 2025-12-04 | criteria provided, single submitter | clinical testing | The c.203_204delTG variant in HBB is a frameshift variant predicted to shift the reading frame beginning at codon 68 and leads to a stop codon 5 codons downstream. 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: 8257991). Given the available evidence, this variant is classified as Pathogenic. |
| Gene |
RCV000508401 | SCV005685643 | pathogenic | not provided | 2025-09-12 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 8257991, 27756326) |
| Fulgent Genetics, |
RCV002496454 | SCV002813817 | 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 | 2021-11-24 | criteria provided, single submitter | clinical testing | |
| Clinical Genetics and Genomics, |
RCV000508401 | SCV001449703 | pathogenic | not provided | 2018-01-23 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV000508401 | SCV001158004 | pathogenic | not provided | 2025-03-26 | criteria provided, single submitter | clinical testing | The HBB c.203_204delTG; p.Val68AlafsTer5 variant (rs34282684, HbVar ID: 868), also known as Codon 67 (-TG), is reported in the literature in an individual with beta-thalassemia major in trans to a whole-gene HBB deletion (Eng 1993). The c.203_204delTG variant was also observed in heterozygous relatives with hematological profiles consistent with beta-thalassemia minor (Eng 1993). This variant is reported in ClinVar (Variation ID: 36303) and is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This variant causes a frameshift by deleting two nucleotides, so it 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 Eng B et al. Identification of two novel beta zero-thalassemia mutations in a Filipino family: frameshift codon 67 (-TG) and a beta-globin gene deletion. Hum Mutat. 1993;2(5):375-9. PMID: 8257991 |
| Labcorp Genetics |
RCV000508401 | SCV000949031 | pathogenic | not provided | 2023-12-24 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Val68Alafs*5) in the HBB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HBB are known to be pathogenic (PMID: 23637309). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with beta thalassemia (PMID: 8257991). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 36303). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000590298 | SCV000697091 | pathogenic | beta Thalassemia | 2024-10-02 | criteria provided, single submitter | clinical testing | Variant summary: HBB c.203_204delTG (p.Val68AlafsX5) 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. The frequency data for this variant in gnomAD is considered unreliable, as metrics indicate poor data quality at this position. c.203_204delTG has been reported in the literature in at least one individual affected with Beta Thalassemia (e.g. Eng_1993). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication was ascertained in the context of this evaluation (PMID: 8257991). ClinVar contains an entry for this variant (Variation ID: 36303). Based on the evidence outlined above, the variant was classified as pathogenic. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000508401 | SCV000601257 | pathogenic | not provided | 2025-08-15 | criteria provided, single submitter | clinical testing | The HBB c.203_204del (p.Val68Alafs*5) variant (also known as codon 67 (-TG)) alters the translational reading frame of the HBB mRNA and causes the premature termination of HBB protein synthesis. This variant has been reported in the compound heterozygous state in an individual with beta-thalassemia major (PMID: 8257991 (1993), HbVar (http://globin.bx.psu.edu/cgi-bin/hbvar/counter)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as pathogenic. |
| Counsyl | RCV005430469 | SCV001132414 | likely pathogenic | Beta-thalassemia HBB/LCRB | 2015-11-16 | no assertion criteria provided | clinical testing | This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. |