Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Integrated Genetics/Laboratory Corporation of America | RCV000029971 | SCV000052626 | pathogenic | Beta thalassemia major | 2011-08-18 | criteria provided, single submitter | curation | Converted during submission to Pathogenic. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000507807 | SCV000601262 | pathogenic | not provided | 2017-07-10 | criteria provided, single submitter | clinical testing | |
| Integrated Genetics/Laboratory Corporation of America | RCV000169623 | SCV000697101 | pathogenic | beta Thalassemia | 2017-05-24 | criteria provided, single submitter | clinical testing | Variant summary: The HBB c.251delG (p.Gly84Alafs) variant results in a premature termination codon, predicted to cause a truncated or absent HBB 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. c.287dupA, p.Leu97fs). The variant of interest has not been found in a large and broad control population from ExAC in 121390 control chromosomes. This variant was reported in patients with beta thalassemia in a homozygous state as well compound heterozygotes with other pathogenic variants, including evidence of cosegregation with disease (El-Kalla_1997, Rahimi_2010, Al-Allawi_2014, and Ulasli_2015). In an Iraqi study that included 74 beta thalassemia patients, it was found in nine patients and was the third most common mutation (Al-Allawi_2014). In another Iranian study that included 185 beta thalassemia patients, its allele frequency was 1.08% (Rahimi_2010). Available data including clinical and biochemical picture of heterozygous carriers supports that this variant causes transfusion-dependent thalassemia in a homozygous state or in a compound heterozygous state with another severe (beta0) variant. Multiple clinical diagnostic laboratories/reputable databases have classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. |
| Invitae | RCV000507807 | SCV001374567 | pathogenic | not provided | 2019-05-16 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gly84Alafs*6) in the HBB gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with beta thalassemia (PMID: 24719849, 2525253, 28670940, 27756326). This variant is also known as 250delG and 82/83 (-G) in the literature. ClinVar contains an entry for this variant (Variation ID: 36306). Loss-of-function variants in HBB are known to be pathogenic (PMID: 23637309). For these reasons, this variant has been classified as Pathogenic. |
| Counsyl | RCV000169623 | SCV000221151 | pathogenic | beta Thalassemia | 2015-11-16 | no assertion criteria provided | clinical testing | |
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RCV000169623 | SCV001244555 | pathogenic | beta Thalassemia | 2019-11-25 | no assertion criteria provided | curation |