ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.*110_*111del (rs63750205)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000780307 SCV000917474 likely pathogenic beta Thalassemia 2018-12-20 criteria provided, single submitter clinical testing Variant summary: HBB c.*110_*111delTA is located in the untranslated mRNA region downstream of the termination codon that lies in the 'known' polyA tail signal (AATAAA) of HBB, and mutations in this region are known to reduce the synthesis of mRNA. Therefore, this variant is expected or likely to interfere with cleavage of transcript and addition of polyA tail, leading to an elongated transcript that is unstable (Orkin 1985). To support this notion, MutationTaster also predicts the variant to be disease-causing. The variant was absent in 30966 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.*110_*111delTA has been reported twice in literature, one individual diagnosed with BTHAL and one individual having typical features of BTHAL minor (Ghanem_1992, Kimberland_1995). Ithanet lists variant as a "Globin gene causative mutation". In the same region, a variant c.*110T>C and c.*111A>G have been reported in literature as a common pathogenic variant. 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 likely pathogenic.
The ITHANET community portal, The Cyprus Institute of Neurology and Genetics RCV000780307 SCV001244460 pathogenic beta Thalassemia 2019-11-25 no assertion criteria provided curation

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