ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.251del (p.Gly84fs) (rs193922555)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169623 SCV000221151 likely pathogenic beta Thalassemia 2015-02-23 criteria provided, single submitter literature only
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.
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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000507807 SCV000601262 pathogenic not provided 2017-07-10 criteria provided, single submitter clinical testing

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