ClinVar Miner

Submissions for variant NM_183050.4(BCKDHB):c.487G>T (p.Glu163Ter)

dbSNP: rs1057516799
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000409047 SCV000486238 pathogenic Maple syrup urine disease 2016-04-22 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000780960 SCV000918643 pathogenic Maple syrup urine disease type 1B 2018-10-18 criteria provided, single submitter clinical testing Variant summary: BCKDHB c.487G>T (p.Glu163X) 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 was absent in 277258 control chromosomes (gnomAD and publication). The variant, c.487G>T, has been reported in the literature in multiple individuals (compound heterozygotes and homozygotes) affected with Maple Syrup Urine Disease Type 1B (Hallam_2014, Rodriguez-Pombo_2006). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity (Fisher_1993). A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cite variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Genome-Nilou Lab RCV000409047 SCV002033146 pathogenic Maple syrup urine disease 2021-11-07 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000409047 SCV002238420 pathogenic Maple syrup urine disease 2022-10-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu163*) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with maple syrup urine disease (PMID: 16786533). ClinVar contains an entry for this variant (Variation ID: 370827). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000409047 SCV004215990 pathogenic Maple syrup urine disease 2023-04-04 criteria provided, single submitter clinical testing
Natera, Inc. RCV000780960 SCV002077436 pathogenic Maple syrup urine disease type 1B 2020-10-01 no assertion criteria provided clinical testing

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