ClinVar Miner

Submissions for variant NM_183050.4(BCKDHB):c.348del (p.Asp117fs)

dbSNP: rs1400121541
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000548346 SCV000627816 pathogenic Maple syrup urine disease 2024-11-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asp117Ilefs*113) 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 (no rsID available, gnomAD 0.009%). This premature translational stop signal has been observed in individuals with maple syrup urine disease (PMID: 16786533, 26232051). ClinVar contains an entry for this variant (Variation ID: 457148). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000548346 SCV001362117 pathogenic Maple syrup urine disease 2019-09-16 criteria provided, single submitter clinical testing Variant summary: BCKDHB c.348delA (p.Asp117IlefsX113) 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 (eg. c.853C>T, p.Arg285X; c.970C>T, p.Arg324X). The variant allele was found at a frequency of 1.6e-05 in 250924 control chromosomes (gnomAD). c.348delA has been reported in the literature in compound heterozygous and homozygous individuals affected with Maple syrup urine disease (Couce_2015, Rodriguez-Pombo_2006). These data indicate that the variant may be associated with disease. Enzymatic activity in an individual homozygous for the variant was determined to be 14% and in an individual compound heterozygous for the variant and another variant was determined to be 1.3%. A ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Genome-Nilou Lab RCV000548346 SCV002033142 pathogenic Maple syrup urine disease 2021-11-07 criteria provided, single submitter clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV000548346 SCV003807965 pathogenic Maple syrup urine disease 2022-11-10 criteria provided, single submitter clinical testing ACMG classification criteria: PVS1 very strong, PM2 supporting, PM3 strong, PP4
Baylor Genetics RCV004568730 SCV004215984 pathogenic Maple syrup urine disease type 1A 2024-01-12 criteria provided, single submitter clinical testing
Natera, Inc. RCV001834748 SCV002077431 pathogenic Maple syrup urine disease type 1B 2021-05-24 no assertion criteria provided clinical testing

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