ClinVar Miner

Submissions for variant NM_183050.4(BCKDHB):c.93_103dup (p.Phe35fs)

dbSNP: rs398124601
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169513 SCV000220982 likely pathogenic Maple syrup urine disease 2014-12-23 criteria provided, single submitter literature only
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589099 SCV000700013 pathogenic Maple syrup urine disease type 1B 2020-07-27 criteria provided, single submitter clinical testing Variant summary: BCKDHB c.93_103dup11 (p.Phe35TrpfsX41) 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 was absent in 198414 control chromosomes (gnomAD). c.93_103dup11 has been reported in the literature in individuals affected with Maple Syrup Urine Disease (Rodr-guez-Pombo_2006, Cheng_2017, Li_2018). These data indicate that the variant may 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%-<30% of normal BCKD activity (Rodr-guez-Pombo_2006). One ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000169513 SCV001204718 pathogenic Maple syrup urine disease 2024-01-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Phe35Trpfs*41) 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, 29307017). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as c.92_102dup11. ClinVar contains an entry for this variant (Variation ID: 189101). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV000169513 SCV002017796 pathogenic Maple syrup urine disease 2021-05-01 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000169513 SCV002033136 likely pathogenic Maple syrup urine disease 2021-11-07 criteria provided, single submitter clinical testing
Baylor Genetics RCV000169513 SCV004215979 pathogenic Maple syrup urine disease 2023-06-01 criteria provided, single submitter clinical testing
Natera, Inc. RCV000589099 SCV002077422 pathogenic Maple syrup urine disease type 1B 2020-11-09 no assertion criteria provided clinical testing

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