Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000759794 | SCV000889365 | likely pathogenic | not provided | 2020-11-05 | criteria provided, single submitter | clinical testing | To the best of our knowledge, the variant has not been reported in the published literature. However, this variant alters the translational reading frame of the HBB mRNA and is predicted to cause the premature termination of HBB protein synthesis. As a result, it prevents the inclusion of important functional domains in any synthesized HBB protein. Therefore, we predict that this variant is likely pathogenic. |
| Invitae | RCV000759794 | SCV001588757 | pathogenic | not provided | 2020-03-18 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the HBB protein. Other variant(s) that disrupt this region (p.Asn109Glnfs*32) have been determined to be pathogenic (PMID: 1728311, 1897518, 3683554, 9401495). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has not been reported in the literature in individuals with HBB-related conditions. ClinVar contains an entry for this variant (Variation ID: 619856). This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the HBB gene (p.Leu76Trpfs*17). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 72 amino acids of the HBB protein. |