Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000506185 | SCV000601289 | pathogenic | not provided | 2022-10-12 | criteria provided, single submitter | clinical testing | The HBB c.323dup (p.Asn109Glnfs*32) frameshift variant alters the translational reading frame of the HBB mRNA and causes the premature termination of HBB protein synthesis. In the published literature, the variant has been reported in individuals with beta-thalassemia (PMID: 3683554 (1987), 23590658 (2013)). Based on the available information, this variant is classified as pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000589491 | SCV000697119 | pathogenic | beta Thalassemia | 2017-07-03 | criteria provided, single submitter | clinical testing | Variant summary: The c.323dupG (p.Asn109Glnfs) variant in HBB gene is a frameshift change that is predicted to cause loss of normal protein function through protein truncation or nonsense-mediated mRNA decay. The variant is absent from the large control population dataset of ExAC, but is present at a low frequency in gnomAD dataset (0.000007; 2/276928 chrs tested), which does not exceed exceed the estimated maximal expected allele frequency of a pathogenic variant (0.011). The variant has been reported in several affected individuals presented with b-thalassemia major via published reports and is cited by reputable databases/clinical laboratories as Pathogenic. Taking together, the variant was classified as Pathogenic. |
| Invitae | RCV000506185 | SCV001384504 | pathogenic | not provided | 2023-02-22 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asn109Glnfs*32) in the HBB gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 39 amino acid(s) of the HBB protein. This variant is present in population databases (rs606231216, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with HBB-related conditions (PMID: 3683554). ClinVar contains an entry for this variant (Variation ID: 439153). This variant disrupts a region of the HBB protein in which other variant(s) (p.Val127Glufs*8) have been determined to be pathogenic (PMID: 8535446, 31190580). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| ARUP Laboratories, |
RCV000506185 | SCV002048071 | pathogenic | not provided | 2023-10-13 | criteria provided, single submitter | clinical testing | The HBB c.323dupG; p.Asn109GlnfsTer32 variant (rs35225141, HbVar ID: 945), also known as c.321_322insG and Codon 106/107 (+G), has been reported in individuals with beta(0) thalassemia (Hoppe 2013), and found with another pathogenic HBB variant (Wong 1987). This variant is reported as pathogenic in ClinVar (Variation ID: 439153). It is only observed on two alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. This variant causes a frameshift by duplicating a single nucleotide, 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 Hoppe CC. Prenatal and newborn screening for hemoglobinopathies. Int J Lab Hematol. 2013 Jun;35(3):297-305. PMID: 23590658. Wong C et al. Characterization of beta-thalassaemia mutations using direct genomic sequencing of amplified single copy DNA. Nature. 1987 Nov 26-Dec 2;330(6146):384-6. PMID: 3683554. |
| OMIM | RCV000016668 | SCV000036938 | pathogenic | Beta zero thalassemia | 1987-11-26 | no assertion criteria provided | literature only | |
| The ITHANET community portal, |
RCV000589491 | SCV001244495 | pathogenic | beta Thalassemia | 2019-11-25 | no assertion criteria provided | curation |