Total submissions: 7
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 |
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, |
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- |
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, |
RCV001826771 | SCV002079876 | pathogenic | Maple syrup urine disease type 1B | 2020-07-13 | no assertion criteria provided | clinical testing |