Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000169441 | SCV000220858 | likely pathogenic | beta Thalassemia | 2014-11-06 | criteria provided, single submitter | literature only | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000508423 | SCV000601323 | pathogenic | not provided | 2021-07-01 | criteria provided, single submitter | clinical testing | The HBB c.85dup (p.Leu29Profs*16) pathogenic variant is a frameshift mutation that causes the premature termination of beta globin protein synthesis and is associated with beta-zero-thalassemia (PMID: 2014803 (1991)). |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000780308 | SCV000917475 | pathogenic | Hemoglobinopathy | 2018-04-27 | criteria provided, single submitter | clinical testing | Variant summary: HBB c.85dupC (p.Leu29ProfsX16) 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 variant was absent in 277176 control chromosomes (gnomAD and publications). The variant, c.85dupC, has been reported in the literature in multiple individuals affected with Beta Thalassemia Major. 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. Multiple ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cites variant as "pathogenic." Based on the evidence outlined above, the variant was classified as pathogenic. |
Invitae | RCV000508423 | SCV000953848 | pathogenic | not provided | 2024-01-05 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu29Profs*16) 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 individuals with beta thalassaemia (PMID: 1850955, 2014803). This variant is also known as 27-28insC. ClinVar contains an entry for this variant (Variation ID: 15432). For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV001004352 | SCV001163287 | pathogenic | Hb SS disease | criteria provided, single submitter | clinical testing | ||
ARUP Laboratories, |
RCV000508423 | SCV004562346 | pathogenic | not provided | 2023-09-04 | criteria provided, single submitter | clinical testing | The HBB c.85dup; p.Leu29ProfsTer16 variant (also known as Codons 27/28 (+C), rs35532010, HbVar ID: 810) is reported in the literature in multiple individuals affected with beta-thalassemia major in the compound heterozygous state with another pathogenic HBB variant (Lin 1991, Liu 2011, HbVar and references therein). The p.Leu29ProfsTer16 variant has also been described in beta-thalassemia minor patients without additional reported variants (Liu 2011, HbVar and references therein). This variant is reported as pathogenic/likely pathogenic by several laboratories in ClinVar (Variation ID: 15432), and it is absent the Genome Aggregation Database, indicating it is not a common polymorphism. This variant causes a frameshift by inserting a single nucleotide, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, the p.Leu29ProfsTer16 variant is considered to be pathogenic. References: Link to HbVar database: https://globin.bx.psu.edu/hbvar/menu.html Lin LI et al. The spectrum of beta-thalassemia mutations in Taiwan: identification of a novel frameshift mutation. Am J Hum Genet. 1991 Apr;48(4):809-12. PMID: 2014803. Liu SC et al. Molecular lesion frequency of hemoglobin gene disorders in Taiwan. Hemoglobin. 2011;35(3):228-36. PMID: 21599435. |
OMIM | RCV000016689 | SCV000036959 | pathogenic | Beta zero thalassemia | 2017-12-12 | no assertion criteria provided | literature only | |
The ITHANET community portal, |
RCV000169441 | SCV001244427 | pathogenic | beta Thalassemia | 2019-11-25 | no assertion criteria provided | curation | |
Natera, |
RCV000169441 | SCV002091593 | pathogenic | beta Thalassemia | 2017-03-17 | no assertion criteria provided | clinical testing |