Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000179048 | SCV000231239 | pathogenic | not provided | 2013-08-23 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000811119 | SCV000951369 | pathogenic | Maple syrup urine disease | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 5 of the BCKDHB gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs398124589, gnomAD 0.006%). Disruption of this splice site has been observed in individual(s) with maple syrup urine disease (MSUD) (PMID: 8312380, 27507644). ClinVar contains an entry for this variant (Variation ID: 96602). Studies have shown that disruption of this splice site results in skipping of exons 5-6 and introduces a premature termination codon (PMID: 8312380). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. |
Ce |
RCV000179048 | SCV001250044 | pathogenic | not provided | 2017-07-01 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000811119 | SCV001983715 | pathogenic | Maple syrup urine disease | 2021-09-08 | criteria provided, single submitter | clinical testing | Variant summary: BCKDHB c.633+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.2e-05 in 251150 control chromosomes. c.633+1G>A has been reported in the literature in two individuals affected with Maple Syrup Urine Disease, in the homozygous state (Abiri_2017, Abiri_2019). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Revvity Omics, |
RCV000811119 | SCV002017785 | pathogenic | Maple syrup urine disease | 2019-08-16 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV000811119 | SCV002033154 | pathogenic | Maple syrup urine disease | 2021-11-07 | criteria provided, single submitter | clinical testing | |
National Newborn Screening Laboratory, |
RCV000811119 | SCV002097382 | pathogenic | Maple syrup urine disease | criteria provided, single submitter | clinical testing | This variant is located within the ±2 bp from a splice site in the BCKDHB gene, where loss of function is a known mechanism of disease. It is present in population databases in low frequency (GnomAD exomes: 0,00001; TopMed: 0,00002). This variant has been published in the literature associated with individuals with MSUD (PMID: 27507644, 31119508). It was found in a compound heterozygous state with a known pathogenic variant in a patient with MSUD phenotype. | |
Baylor Genetics | RCV004566968 | SCV004215991 | pathogenic | Maple syrup urine disease type 1A | 2023-12-13 | criteria provided, single submitter | clinical testing |