Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000185796 | SCV000238734 | pathogenic | not provided | 2017-02-15 | criteria provided, single submitter | clinical testing | The c.661_664delTACG pathogenic variant in the BCKDHA gene causes a frameshift starting with codon Tyrosine 221, changes this amino acid to a Glutamine residue and creates a premature Stop codon at position 108 of the new reading frame, denoted p.Tyr221GlnfsX108. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Although this pathogenic variant has not been previously reported to our knowledge, its presence is consistent with a diagnosis of maple syrup urine disease. |
| National Newborn Screening Laboratory, |
RCV000408793 | SCV002097377 | pathogenic | Maple syrup urine disease | criteria provided, single submitter | clinical testing | This is a frame-shift variant in the BCKDHA gene, for which loss of function is a known disease mechanism. This variant results in a truncated protein by creating a premature stop codon. It is not present in population databases (GnomAD exomes, GnomAD genomes). This variant has one publication associated with an individual with MSUD phenotype (PMID: 28417071). It was found in a compound heterozygous state in a patient with biochemical analysis supporting the diagnosis of MSUD (NBS dried blood sample: Xle: 2045umol/L, Val: 554umol/L, Xle/Ala: 7,66. Pre-treatment plasma aminogram: Leu: 2747umol/L, Val: 788umol/L, Ile: 491umol/L, Leu/Ala: 59,7). | |
| Baylor Genetics | RCV000408793 | SCV004215895 | pathogenic | Maple syrup urine disease | 2023-07-17 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000408793 | SCV004649749 | pathogenic | Maple syrup urine disease | 2023-04-12 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 203638). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with autosomal recessive maple syrup urine disease (PMID: 28417071). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr221Glnfs*108) in the BCKDHA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BCKDHA are known to be pathogenic (PMID: 16786533, 22593002). |
| Bioscientia Institut fuer Medizinische Diagnostik Gmb |
RCV000408793 | SCV000484930 | likely pathogenic | Maple syrup urine disease | no assertion criteria provided | clinical testing |