ClinVar Miner

Submissions for variant NM_183050.4(BCKDHB):c.302G>A (p.Gly101Asp)

gnomAD frequency: 0.00001  dbSNP: rs398124571
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000177427 SCV000229283 likely pathogenic not provided 2013-09-04 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001162146 SCV002033062 uncertain significance Maple syrup urine disease 2021-11-07 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001162146 SCV003519633 pathogenic Maple syrup urine disease 2024-02-06 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 101 of the BCKDHB protein (p.Gly101Asp). This variant is present in population databases (rs398124571, gnomAD 0.004%). This missense change has been observed in individual(s) with maple syrup urine disease (PMID: 31980395, 32151765; Invitae). 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: 96576). 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) performed at Invitae indicates that this missense variant is expected to disrupt BCKDHB protein function with a positive predictive value of 80%. This variant disrupts the p.Gly101 amino acid residue in BCKDHB. Other variant(s) that disrupt this residue have been observed in individuals with BCKDHB-related conditions (PMID: 30228974), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Neuberg Centre For Genomic Medicine, NCGM RCV001162146 SCV004176636 likely pathogenic Maple syrup urine disease 2023-02-14 criteria provided, single submitter clinical testing The missense c.302G>A (p.Gly101Asp) variant in BCKDHB gene has been reported in compound heterozygous state in multiple individuals affected with maple syrup urine disease (Pode-Shakked N et al. 2020; Ali EZ et al. 2018). The p.Gly101Asp variant 0.002% in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant has been reported to the ClinVar database as Uncertain Significance / Likely pathogenic. The amino acid change p.Gly101Asp in BCKDHB is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Gly at position 101 is changed to a Asp changing protein sequence and it might alter its composition and physico-chemical properties. Functional studies are required to prove the pathogenicity for the variant, for these reasons, this variant has been classified as Likely Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005031573 SCV005671889 likely pathogenic Maple syrup urine disease type 1B 2024-02-22 criteria provided, single submitter clinical testing

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