ClinVar Miner

Submissions for variant NM_183050.4(BCKDHB):c.1006G>A (p.Gly336Ser)

dbSNP: rs398124560
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000082719 SCV000114763 likely pathogenic not provided 2017-12-07 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000587204 SCV000700009 pathogenic Maple syrup urine disease type 1B 2023-07-05 criteria provided, single submitter clinical testing Variant summary: BCKDHB c.1006G>A (p.Gly336Ser) results in a non-conservative amino acid change located in the C-terminal domain (IPR033248) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251350 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1006G>A has been reported in the literature in multiple homozygous and compound heterozygous individuals affected with Maple Syrup Urine Disease Type 1B (e.g., Imtiaz_2017, Cheng_2017). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 28830848, 28417071). Five submitters have reported clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic (n = 1) or likely pathogenic (n = 4). Based on the evidence outlined above, the variant was classified as pathogenic.
Counsyl RCV000674620 SCV000799989 likely pathogenic Maple syrup urine disease 2018-05-16 criteria provided, single submitter clinical testing
Invitae RCV000674620 SCV000941010 pathogenic Maple syrup urine disease 2023-12-01 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 336 of the BCKDHB protein (p.Gly336Ser). This variant is present in population databases (rs398124560, gnomAD 0.006%). This missense change has been observed in individual(s) with maple syrup urine disease (PMID: 28417071, 28830848, 31112740). ClinVar contains an entry for this variant (Variation ID: 96562). 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 not expected to disrupt BCKDHB protein function with a negative predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000674620 SCV001137188 likely pathogenic Maple syrup urine disease 2019-05-28 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000674620 SCV002033164 likely pathogenic Maple syrup urine disease 2021-11-07 criteria provided, single submitter clinical testing
Baylor Genetics RCV000674620 SCV004215963 pathogenic Maple syrup urine disease 2023-08-30 criteria provided, single submitter clinical testing

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