NM_183050.4(BCKDHB):c.368del (p.Pro123fs) AND Maple syrup urine disease

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Mar 17, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:

Allele description [Variation Report for NM_183050.4(BCKDHB):c.368del (p.Pro123fs)]

NM_183050.4(BCKDHB):c.368del (p.Pro123fs)

BCKDHB:branched chain keto acid dehydrogenase E1 subunit beta [Gene - OMIM - HGNC]
Variant type:
Cytogenetic location:
Genomic location:
Preferred name:
NM_183050.4(BCKDHB):c.368del (p.Pro123fs)
  • NC_000006.12:g.80167702del
  • NG_009775.1:g.66076del
  • NG_009775.2:g.66076del
  • NM_000056.4:c.368del
  • NM_001318975.1:c.158del
  • NM_183050.4:c.368delMANE SELECT
  • NP_000047.1:p.Pro123fs
  • NP_001305904.1:p.Pro53fs
  • NP_898871.1:p.Pro123fs
  • NC_000006.11:g.80877416del
  • NC_000006.11:g.80877419del
  • NM_000056.3:c.368delC
  • NR_134945.2:n.391del
Protein change:
dbSNP: rs1085307058
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000056.4:c.368del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001318975.1:c.158del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_183050.4:c.368del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NR_134945.2:n.391del - non-coding transcript variant - [Sequence Ontology: SO:0001619]


Maple syrup urine disease (MSUD)
Branched chain ketoaciduria; Branched-chain alpha-keto acid dehydrogenase deficiency; Keto acid decarboxylase deficiency
MONDO: MONDO:0009563; MeSH: D008375; MedGen: C0024776; Orphanet: 511; OMIM: 248600; OMIM: PS248600

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000267225Soonchunhyang University Bucheon Hospital,Soonchunhyang University Medical Centercriteria provided, single submitter
Likely pathogenic
(Mar 18, 2016)
germlinereference population

PubMed (2)
[See all records that cite these PMIDs]

SCV001585234Invitaecriteria provided, single submitter
(Mar 17, 2020)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
East Asiangermlineunknown1not providednot providednot providednot providedreference population



Structural and biochemical basis for novel mutations in homozygous Israeli maple syrup urine disease patients: a proposed mechanism for the thiamin-responsive phenotype.

Chuang JL, Wynn RM, Moss CC, Song JL, Li J, Awad N, Mandel H, Chuang DT.

J Biol Chem. 2004 Apr 23;279(17):17792-800. Epub 2004 Jan 23.

PubMed [citation]

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
See all PubMed Citations (5)

Details of each submission

From Soonchunhyang University Bucheon Hospital,Soonchunhyang University Medical Center, SCV000267225.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1East Asian1not providednot providedreference population PubMed (2)
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

From Invitae, SCV001585234.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)


This sequence change creates a premature translational stop signal (p.Pro123Hisfs*107) in the BCKDHB gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BCKDHB-related conditions. ClinVar contains an entry for this variant (Variation ID: 225303). Loss-of-function variants in BCKDHB are known to be pathogenic (PMID: 16786533, 22593002). For these reasons, this variant has been classified as Pathogenic.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 14, 2021

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