ClinVar Miner

Submissions for variant NM_183050.4(BCKDHB):c.392G>T (p.Gly131Val)

dbSNP: rs774472182
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001918259 SCV002179705 pathogenic Maple syrup urine disease 2022-10-24 criteria provided, single submitter clinical testing 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. This variant disrupts the p.Gly131 amino acid residue in BCKDHB. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 29740478, 32193832). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 131 of the BCKDHB protein (p.Gly131Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with maple syrup urine disease (PMID: 31980395, 33955723). ClinVar contains an entry for this variant (Variation ID: 1407094).
Baylor Genetics RCV004571587 SCV005058099 likely pathogenic Maple syrup urine disease type 1A 2024-02-12 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001918259 SCV005077384 pathogenic Maple syrup urine disease 2024-04-05 criteria provided, single submitter clinical testing Variant summary: BCKDHB c.392G>T (p.Gly131Val) results in a non-conservative amino acid change located in the Transketolase-like, pyrimidine-binding domain (IPR005475) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251182 control chromosomes. c.392G>T has been reported in the literature in multiple homozygous and compound heterozygous individuals affected with classic Maple Syrup Urine Disease (e.g. Strauss_2020, Margutti_2020, Campanholi_2021). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 33955723, 33131499, 31980395). ClinVar contains an entry for this variant (Variation ID: 1407094). Based on the evidence outlined above, the variant was classified as pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005038483 SCV005671893 pathogenic Maple syrup urine disease type 1B 2024-04-10 criteria provided, single submitter clinical testing

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