Total submissions: 16
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000762424 | SCV000232360 | pathogenic | not provided | 2015-03-05 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000587416 | SCV000700012 | pathogenic | Maple syrup urine disease type 1B | 2016-07-08 | criteria provided, single submitter | clinical testing | Variant summary: The BCKDHB c.832G>A (p.Gly278Ser) variant involves the alteration of a conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this variant (SNPs&GO not captured due to low reliability index). The G278S substitution exhibits a shift in polarity from non-polar to polar, and G278 is located in the Transketolase C-terminal/Pyruvate-ferredoxin oxidoreductase domain II of the 2-oxoisovalerate dehydrogenase subunit beta protein. Functional studies in fibroblasts from compound heterozygous patients show enzyme activity of <10%. This variant was found in 58/120788 control chromosomes at a frequency of 0.0004802, which does not exceed the estimated maximal expected allele frequency of a pathogenic BCKDHB variant (0.0014639). G278S has been reported in numerous MSUD patients in the literature in compound heterozygous state. Furthermore, at least one clinical diagnostic laboratory classified this variant as pathogenic, and the variant is reported as a commonly known pathogenic variant in the literature. Taken together, this variant is classified as Pathogenic. |
Ce |
RCV000762424 | SCV000892739 | pathogenic | not provided | 2023-08-01 | criteria provided, single submitter | clinical testing | BCKDHB: PM3:Very Strong, PM2, PP4:Moderate, PP3 |
Fulgent Genetics, |
RCV000056009 | SCV000894398 | pathogenic | Maple syrup urine disease | 2022-03-28 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV000056009 | SCV001194015 | likely pathogenic | Maple syrup urine disease | 2019-10-18 | criteria provided, single submitter | clinical testing | NM_183050.2(BCKDHB):c.832G>A(G278S) is classified as likely pathogenic in the context of maple syrup urine disease type Ib and is associated with the intermediate form of this disease. Sources cited for classification include the following: PMID 14567968, 17922217 and 20307994. Classification of NM_183050.2(BCKDHB):c.832G>A(G278S) is based on the following criteria: This variant has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.‚Äã |
Labcorp Genetics |
RCV000056009 | SCV001200782 | pathogenic | Maple syrup urine disease | 2024-01-28 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 278 of the BCKDHB protein (p.Gly278Ser). This variant is present in population databases (rs386834233, gnomAD 0.3%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with BCKDHB-related conditions, some of which present with lab findings that are highly specific for maple syrup urine disease (PMID: 11509994, 14567968, 17922217, 20307994). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 65771). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BCKDHB protein function. For these reasons, this variant has been classified as Pathogenic. |
Centre for Inherited Metabolic Diseases, |
RCV000056009 | SCV001519660 | pathogenic | Maple syrup urine disease | 2021-03-16 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV000056009 | SCV002033158 | pathogenic | Maple syrup urine disease | 2021-11-07 | criteria provided, single submitter | clinical testing | |
National Newborn Screening Laboratory, |
RCV000056009 | SCV002097373 | pathogenic | Maple syrup urine disease | criteria provided, single submitter | clinical testing | This is a missense variant located within exon 7 and generates a change from the aminoacid Glycine to a Serine in position 278. It is present in population databases in low frequency (GnomAD exomes: 0.00055; ExAc: 0.00048). This variant has been published in the literature associated with individuals with MSUD ( PMID: 11509994, PMID: 14517957, PMID: 17922217). | |
Revvity Omics, |
RCV000056009 | SCV003821539 | likely pathogenic | Maple syrup urine disease | 2023-02-17 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000762424 | SCV004034323 | pathogenic | not provided | 2023-09-08 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25087612, 23952016, 11509994, 20307994, 17922217, 31980526, 34426522, 33726816, 14517957) |
Rady Children's Institute for Genomic Medicine, |
RCV000056009 | SCV004046258 | pathogenic | Maple syrup urine disease | criteria provided, single submitter | clinical testing | This variant has been previously reported in multiple individuals with maple syrup urine disease (MSUD) (PMID: 11509994‚ 14517957‚ 17922217, 14567968, 20307994). The c.832G>A (p.Gly278Ser) variant is present in the heterozygous state in the gnomAD population database at a frequency of 0.058% (164/282184). It affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. Based on the available evidence, the c.832G>A (p.Gly278Ser) variant is classified as Pathogenic. | |
Baylor Genetics | RCV004566908 | SCV004215941 | pathogenic | Maple syrup urine disease type 1A | 2024-03-16 | criteria provided, single submitter | clinical testing | |
Laboratory of Medical Genetics, |
RCV000587416 | SCV005052045 | pathogenic | Maple syrup urine disease type 1B | 2024-02-01 | criteria provided, single submitter | curation | |
Gene |
RCV000056009 | SCV000087069 | not provided | Maple syrup urine disease | no assertion provided | literature only | ||
Prevention |
RCV004751250 | SCV005360367 | pathogenic | BCKDHB-related disorder | 2024-05-03 | no assertion criteria provided | clinical testing | The BCKDHB c.832G>A variant is predicted to result in the amino acid substitution p.Gly278Ser. This variant has been reported in the homozygous and compound heterozygous states in multiple individuals with maple syrup urine disease (see for example, Edelmann et al. 2001. PubMed ID: 11509994; Table 2, Flaschker et al. 2007. PubMed ID: 17922217; Puckett et al. 2009. PubMed ID: 20307994). This variant is reported in 0.29% of alleles in individuals of European (Finnish) descent in gnomAD. In vitro experimental studies suggest this variant, in the compound heterozygous state, reduces enzymatic activity (Table 2, Nellis et al. 2003. PubMed ID: 14567968; Table 2, Flaschker et al. 2007. PubMed ID: 17922217). This variant is interpreted as pathogenic. |