ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.112del (p.Trp38fs) (rs63750532)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000508367 SCV000601234 pathogenic not provided 2017-06-29 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781455 SCV000919491 pathogenic Hemoglobinopathy 2018-01-09 criteria provided, single submitter clinical testing Variant summary: The HBB c.112delT (p.Trp38GlyfsX24) 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. This variant is absent in 30964 control chromosomes (gnomAD). Multiple publications have cited the variant in individuals affected with BTHAL, observed predominantly in middle eastern countries (Rund_1991, El-Kalla_1997, Huisman_1997). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001000164 SCV001156652 pathogenic not specified 2019-03-09 criteria provided, single submitter clinical testing The HBB c.112delT; p.Trp38fs variant (rs63750532), also known as Codons 36/37 (-T) or Frameshift 36/37, is described in the literature in individuals with thalassemia who also carried another pathogenic variant (Rund 1991). This variant is reported as pathogenic in ClinVar (15431). It is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant causes a frameshift by deleting a single nucleotide, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. REFERENCES Link to c.112delT variant in HbVar: Rund D et al. Evolution of a genetic disease in an ethnic isolate: beta-thalassemia in the Jews of Kurdistan. Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):310-4.
Baylor Genetics RCV001004345 SCV001163280 pathogenic Hb SS disease criteria provided, single submitter clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV001078307 SCV001251903 pathogenic beta Thalassemia 2020-05-03 criteria provided, single submitter clinical testing
OMIM RCV000016688 SCV000036947 pathogenic beta^0^ Thalassemia 1991-01-01 no assertion criteria provided literature only
The ITHANET community portal, The Cyprus Institute of Neurology and Genetics RCV001078307 SCV001244471 pathogenic beta Thalassemia 2019-11-25 no assertion criteria provided curation

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