NM_001918.4(DBT):c.670G>T (p.Glu224Ter) AND not provided

Clinical significance:Pathogenic (Last evaluated: Oct 25, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000079951.7

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]
Observations:
8

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000231639EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Pathogenic
(Aug 23, 2013)
germlineclinical testing

Citation Link,

SCV000680731GeneDxcriteria provided, single submitter
Pathogenic
(Oct 25, 2018)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown8not providednot providednot providednot providedclinical testing

Details of each submission

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000231639.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided8not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided8not providednot providednot provided

From GeneDx, SCV000680731.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The E224X nonsense variant in the DBT gene has been previously reported in multiple patients with classic maple syrup urine disease (MSUD), both in the homozygous state and in the presence of a second pathogenic variant (Fisher et al., 1993). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. This is supported by functional studies which demonstrate that cell lines with E224X variant result in a markedly truncated polypeptide compared with full-length wildtype (Fisher et al., 1993). In summary, we interpret E224X as pathogenic.

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

Last Updated: May 10, 2021

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