NM_001918.4(DBT):c.670G>T (p.Glu224Ter) AND Maple syrup urine disease

Clinical significance:Pathogenic (Last evaluated: Oct 20, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000179397.10

Allele description [Variation Report for NM_001918.4(DBT):c.670G>T (p.Glu224Ter)]

NM_001918.4(DBT):c.670G>T (p.Glu224Ter)

Gene:
DBT:dihydrolipoamide branched chain transacylase E2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p21.2
Genomic location:
Preferred name:
NM_001918.4(DBT):c.670G>T (p.Glu224Ter)
HGVS:
  • NC_000001.11:g.100216085C>A
  • NG_011852.2:g.38769G>T
  • NM_001918.4:c.670G>T
  • NP_001909.3:p.Glu224Ter
  • NC_000001.10:g.100681641C>A
  • NM_001918.2:c.670G>T
  • NM_001918.3:c.670G>T
  • NP_001909.3:p.Glu224*
Protein change:
E224*
Links:
dbSNP: rs74103423
NCBI 1000 Genomes Browser:
rs74103423
Molecular consequence:
  • NM_001918.4:c.670G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Maple syrup urine disease (MSUD)
Synonyms:
Branched chain ketoaciduria; Branched-chain alpha-keto acid dehydrogenase deficiency; Keto acid decarboxylase deficiency
Identifiers:
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)
OriginMethodCitations
SCV000485927Counsylno assertion criteria providedLikely pathogenic
(Nov 3, 2016)
unknownclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV000834968Invitaecriteria provided, single submitter
Pathogenic
(Oct 20, 2020)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV000893167Fulgent Genetics,Fulgent Geneticscriteria provided, single submitter
Pathogenic
(Oct 31, 2018)
unknownclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Occurrence of a 2-bp (AT) deletion allele and a nonsense (G-to-T) mutant allele at the E2 (DBT) locus of six patients with maple syrup urine disease: multiple-exon skipping as a secondary effect of the mutations.

Fisher CW, Fisher CR, Chuang JL, Lau KS, Chuang DT, Cox RP.

Am J Hum Genet. 1993 Feb;52(2):414-24.

PubMed [citation]
PMID:
8430702
PMCID:
PMC1682180

Production and characterization of murine models of classic and intermediate maple syrup urine disease.

Homanics GE, Skvorak K, Ferguson C, Watkins S, Paul HS.

BMC Med Genet. 2006 Mar 31;7:33.

PubMed [citation]
PMID:
16579849
PMCID:
PMC1448208
See all PubMed Citations (5)

Details of each submission

From Counsyl, SCV000485927.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV000834968.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Glu224*) in the DBT gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs74103423, ExAC 0.1%). This variant has been reported in individuals affected with maple syrup urine disease (PMID: 8430702). ClinVar contains an entry for this variant (Variation ID: 94009). Loss-of-function variants in DBT are known to be pathogenic (PMID: 16579849, 16786533). For these reasons, this variant has been classified as Pathogenic.

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

From Fulgent Genetics,Fulgent Genetics, SCV000893167.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 10, 2021

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