Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000780312 | SCV000917479 | pathogenic | Hemoglobinopathy | 2018-05-04 | criteria provided, single submitter | clinical testing | Variant summary: HBB c.45dupG (p.Trp16ValfsX8) 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 (e.g., p.Lys18fsX2 and p.Glu27X). The variant allele was found at a frequency of 4.1e-06 in 245968 control chromosomes. c.45dupG has been reported in the literature in multiple individuals affected with Beta Thalassemia and is referred to in the literature as a common Chinese mutation (Chan_1988, Lin_2014). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. |
Invitae | RCV003556029 | SCV004294110 | pathogenic | not provided | 2023-06-27 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 15426). This variant is also known as insertion of G between codon 14/15 or c.45_46insG. This premature translational stop signal has been observed in individual(s) with autosomal recessive beta-thalassemia (PMID: 2901867, 28671035, 33092414). This variant is present in population databases (rs35383398, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Trp16Valfs*8) 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). |
OMIM | RCV000016683 | SCV000036953 | pathogenic | Beta zero thalassemia | 1988-10-01 | no assertion criteria provided | literature only | |
The ITHANET community portal, |
RCV001078383 | SCV001244581 | pathogenic | beta Thalassemia | 2019-11-25 | no assertion criteria provided | curation | |
Natera, |
RCV001078383 | SCV002091605 | pathogenic | beta Thalassemia | 2017-03-17 | no assertion criteria provided | clinical testing |