Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
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, |
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; RodrÃguez-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, |
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- |
RCV000179041 | SCV002033152 | pathogenic | Maple syrup urine disease | 2021-11-07 | criteria provided, single submitter | clinical testing | |
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, |
RCV000780959 | SCV001455534 | pathogenic | Maple syrup urine disease type 1B | 2020-09-16 | no assertion criteria provided | clinical testing |