ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.51del (p.Lys18fs) (rs35662066)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724162 SCV000224234 pathogenic not provided 2015-02-10 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000590756 SCV000697137 pathogenic Hemoglobinopathy 2016-10-31 criteria provided, single submitter clinical testing Variant summary: The HBB c.51delC (p.Lys18Argfs) 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.85dupC, c.135delC). Mutation taster predicts a damaging outcome for this variant. This variant was found in 4/121395 control chromosomes at a frequency of 0.000033, which does not exceed the estimated maximal expected allele frequency of a pathogenic HBB variant (0.0111803). It was reported in several BTHAL patients some of whom were homologous for the variant indicating causality. 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 RCV000724162 SCV000885547 pathogenic not provided 2017-11-24 criteria provided, single submitter clinical testing
Myriad Women's Health, Inc. RCV000173145 SCV001194166 pathogenic beta Thalassemia 2019-12-17 criteria provided, single submitter clinical testing NM_000518.4(HBB):c.51delC(K18Rfs*2) is classified as pathogenic in the context of Hb beta chain-related hemoglobinopathy and is associated with beta thalassemia. Sources cited for classification include the following: PMID 18294253, 6714226 and 21389146. Classification of NM_000518.4(HBB):c.51delC(K18Rfs*2) is based on the following criteria: The variant causes a premature termination codon that is expected to be targeted by nonsense-mediated mRNA decay and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening.
Invitae RCV000724162 SCV001210575 pathogenic not provided 2019-07-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys18Argfs*2) in the HBB gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs35662066, ExAC 0.02%). This variant has been observed in individuals affected with beta-thalassemia (PMID: 12403498, 12368169, 27263053). This variant is also known as Codon 16 (-C) in the literature. ClinVar contains an entry for this variant (Variation ID: 15414). Loss-of-function variants in HBB are known to be pathogenic (PMID: 23637309). For these reasons, this variant has been classified as Pathogenic.
Centogene AG - the Rare Disease Company RCV000173145 SCV001424434 pathogenic beta Thalassemia criteria provided, single submitter clinical testing
OMIM RCV000016670 SCV000036940 pathogenic beta^0^ Thalassemia 2017-02-27 no assertion criteria provided literature only
The ITHANET community portal, The Cyprus Institute of Neurology and Genetics RCV000173145 SCV001244647 pathogenic beta Thalassemia 2019-11-25 no assertion criteria provided curation

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