ClinVar Miner

Submissions for variant NM_183050.4(BCKDHB):c.595_596del (p.Ser199_Pro200insTer)

dbSNP: rs398124587
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000790691 SCV000231231 pathogenic not provided 2013-08-23 criteria provided, single submitter clinical testing
Invitae RCV000179041 SCV000627820 pathogenic Maple syrup urine disease 2022-08-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Pro200*) in the BCKDHB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BCKDHB are known to be pathogenic (PMID: 16786533, 22593002). This variant is present in population databases (rs764738271, gnomAD 0.006%). This premature translational stop signal has been observed in individuals with maple syrup urine disease (PMID: 14517957, 18378174, 24791375, 26232051). ClinVar contains an entry for this variant (Variation ID: 96599). For these reasons, this variant has been classified as Pathogenic.
Illumina Laboratory Services, Illumina RCV000179041 SCV000916167 pathogenic Maple syrup urine disease 2016-10-28 criteria provided, single submitter clinical testing The BCKDHB c.595_596delAG (p.Pro200Ter) variant is a frameshift variant that is predicted to result in premature termination of the protein. This variant has been identified in at least nine patients with maple syrup urine disease (MSUD), including in one patient in a homozygous state and in eight patients in a compound heterozygous state (Henneke et al. 2003; Rodríguez-Pombo et al. 2006; Quental et al. 2008; Couce et al. 2015; Feier et al. 2016). Across the available literature, this variant was absent from 150 controls. The p.Pro200Ter variant is reported at a frequency of 0.00012 in the European American population of the Exome Sequencing Project, which is based on only one allele in an area of good sequence coverage so the variant is presumed to be rare. Many patients identified with this variant were described as having a classic MSUD phenotype, exhibiting significantly reduced BCKD enzyme activity when compared to controls. Based on the evidence, the p.Pro200Ter variant is classified as pathogenic for maple syrup urine disease. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000780959 SCV000918642 pathogenic Maple syrup urine disease type 1B 2018-09-10 criteria provided, single submitter clinical testing Variant summary: BCKDHB c.595_596delAG (p.Pro200X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 2.5e-05 in 277088 control chromosomes (gnomAD). c.595_596delAG has been reported in the literature in multiple individuals affected with Maple Syrup Urine Disease Type 1B (e.g. Henneke 2003, Rodriguez-Pombo 2006). These data indicate that the variant is very likely to be associated with disease. At least two publications reported experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity (Henneke 2003, Rodriguez-Pombo 2006). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Genome-Nilou Lab RCV000179041 SCV002033152 pathogenic Maple syrup urine disease 2021-11-07 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000179041 SCV002787822 pathogenic Maple syrup urine disease 2021-07-16 criteria provided, single submitter clinical testing
Baylor Genetics RCV000179041 SCV004215950 pathogenic Maple syrup urine disease 2023-09-26 criteria provided, single submitter clinical testing
Counsyl RCV000179041 SCV001132139 likely pathogenic Maple syrup urine disease 2014-01-02 no assertion criteria provided clinical testing
Natera, Inc. RCV000780959 SCV001455534 pathogenic Maple syrup urine disease type 1B 2020-09-16 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.