ClinVar Miner

Submissions for variant NM_183050.4(BCKDHB):c.799C>T (p.Gln267Ter)

gnomAD frequency: 0.00001  dbSNP: rs398124594
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169389 SCV000220781 likely pathogenic Maple syrup urine disease 2014-10-17 criteria provided, single submitter literature only
Eurofins Ntd Llc (ga) RCV000790821 SCV000232363 pathogenic not provided 2013-08-23 criteria provided, single submitter clinical testing
Invitae RCV000169389 SCV000827980 pathogenic Maple syrup urine disease 2023-10-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln267*) 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 (rs398124594, gnomAD 0.003%). This premature translational stop signal has been observed in individuals with maple syrup urine disease (PMID: 14567968, 16786533, 18378174). ClinVar contains an entry for this variant (Variation ID: 96609). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000169389 SCV001363135 pathogenic Maple syrup urine disease 2019-10-24 criteria provided, single submitter clinical testing Variant summary: BCKDHB c.799C>T (p.Gln267X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 8e-06 in 251058 control chromosomes (gnomAD). c.799C>T has been reported in the literature in multiple compound heterozygous and homozygous individuals affected with Maple syrup urine disease (Nellis_2003, Rodriguez-Pombo_2006, Quental_2008, Thevenon_2014). These data indicate that the variant is very likely to be associated with disease. At least two publication reported this variant results in <10% of normal activity (Nellis_2003, Rodriguez-Pombo_2006). One ClinVar submitter (evaluation after 2014) cited the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Genome-Nilou Lab RCV000169389 SCV002033157 pathogenic Maple syrup urine disease 2021-11-07 criteria provided, single submitter clinical testing
Baylor Genetics RCV000169389 SCV004215948 pathogenic Maple syrup urine disease 2023-10-10 criteria provided, single submitter clinical testing
Natera, Inc. RCV001826771 SCV002079876 pathogenic Maple syrup urine disease type 1B 2020-07-13 no assertion criteria provided clinical testing

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