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NM_000365.6(TPI1):c.315G>C (p.Glu105Asp)

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Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
3 (Most recent: Mar 21, 2019)
Last evaluated:
Dec 17, 2018
Accession:
VCV000012468.4
Variation ID:
12468
Description:
single nucleotide variant
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NM_000365.6(TPI1):c.315G>C (p.Glu105Asp)

Allele ID
27507
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
12p13.31
Genomic location
12: 6869174 (GRCh38) GRCh38 UCSC
12: 6978338 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
P60174:p.Glu142Asp
NC_000012.11:g.6978338G>C
NC_000012.12:g.6869174G>C
... more HGVS
Protein change
E142D, E105D, E23D
Other names
E104D
Canonical SPDI
NC_000012.12:6869173:G:C
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00012
The Genome Aggregation Database (gnomAD), exomes 0.00008
Trans-Omics for Precision Medicine (TOPMed) 0.00011
The Genome Aggregation Database (gnomAD) 0.00006
Exome Aggregation Consortium (ExAC) 0.00008
Links
ClinGen: CA122423
UniProtKB: P60174#VAR_007536
OMIM: 190450.0001
dbSNP: rs121964845
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 3 criteria provided, multiple submitters, no conflicts Dec 17, 2018 RCV000013284.30
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
TPI1 - - GRCh38
GRCh37
59 109

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Dec 17, 2018)
criteria provided, single submitter
Method: clinical testing
Triosephosphate isomerase deficiency
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV000914600.1
Submitted: (Feb 01, 2019)
Evidence details
Publications
PubMed (10)
Comment:
The TPI1 c.315G>C (p.Glu105Asp) missense variant, which is also referred to as p.Glu104Asp, is a well-known and common disease-associated variant, accounting for approximately 80% of … (more)
Pathogenic
(Dec 17, 2018)
criteria provided, single submitter
Method: clinical testing
Triosephosphate isomerase deficiency
(Autosomal recessive inheritance)
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000967685.1
Submitted: (Mar 21, 2019)
Evidence details
Publications
PubMed (10)
Comment:
The p.Glu142Asp (also known as p.Glu105Asp or p.Glu104Asp) variant in TPI1 has b een reported in at least 10 homozygous and 4 compound heterozygous individuals … (more)
Pathogenic
(Jan 01, 1997)
no assertion criteria provided
Method: literature only
TRIOSEPHOSPHATE ISOMERASE DEFICIENCY
Allele origin: germline
OMIM
Accession: SCV000033531.5
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (5)
Rodriguez-Almazan, C., Arreola, R.,  (more...)

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Child Neurology: Triosephosphate isomerase deficiency. Harris C Neurology 2020 PMID: 32873690
Chromosomal microarray in a highly consanguineous population: diagnostic yield, utility of regions of homozygosity, and novel mutations. Alabdullatif MA Clinical genetics 2017 PMID: 27717089
Whole Exome Sequencing in Pediatric Neurology Patients: Clinical Implications and Estimated Cost Analysis. Nolan D Journal of child neurology 2016 PMID: 26863999
Hemolytic anemia and progressive neurologic impairment: think about triosephosphate isomerase deficiency. Aissa K Fetal and pediatric pathology 2014 PMID: 24840153
Mild hemolytic anemia, progressive neuromotor retardation and fatal outcome: a disorder of glycolysis, triose- phosphate isomerase deficiency. Sarper N The Turkish journal of pediatrics 2013 PMID: 24192681
The E104D mutation increases the susceptibility of human triosephosphate isomerase to proteolysis. Asymmetric cleavage of the two monomers of the homodimeric enzyme. De La Mora-De La Mora I Biochimica et biophysica acta 2013 PMID: 24056040
Triose phosphate isomerase deficiency associated with two novel mutations in TPI gene. Fermo E European journal of haematology 2010 PMID: 20374271
Structural basis of human triosephosphate isomerase deficiency: mutation E104D is related to alterations of a conserved water network at the dimer interface. Rodríguez-Almazán C The Journal of biological chemistry 2008 PMID: 18562316
Triose phosphate isomerase deficiency is caused by altered dimerization--not catalytic inactivity--of the mutant enzymes. Ralser M PloS one 2006 PMID: 17183658
Triosephosphate isomerase deficiency with elevated sweat chloride test: report of a case. Yenicesu I The Turkish journal of pediatrics 2000 PMID: 11196750
Triose phosphate isomerase deficiency in 3 French families: two novel null alleles, a frameshift mutation (TPI Alfortville) and an alteration in the initiation codon (TPI Paris). Valentin C Blood 2000 PMID: 10910933
Triosephosphate isomerase deficiency in a child with congenital hemolytic anemia and severe hypotonia. Linarello RE Pediatric hematology and oncology 1998 PMID: 9842650
Evidence for founder effect of the Glu104Asp substitution and identification of new mutations in triosephosphate isomerase deficiency. Arya R Human mutation 1997 PMID: 9338582
Triosephosphate isomerase deficiency: biochemical and molecular genetic analysis for prenatal diagnosis. Pekrun A Clinical genetics 1995 PMID: 7628118
Triosephosphate isomerase deficiency: repetitive occurrence of point mutation in amino acid 104 in multiple apparently unrelated families. Schneider A American journal of hematology 1995 PMID: 7485100
Human triosephosphate isomerase deficiency resulting from mutation of Phe-240. Chang ML American journal of human genetics 1993 PMID: 8503454
Human triose-phosphate isomerase deficiency: a single amino acid substitution results in a thermolabile enzyme. Daar IO Proceedings of the National Academy of Sciences of the United States of America 1986 PMID: 2876430
Rodriguez-Almazan, C., Arreola, R., Rodriguez-Larrea, D., Aguirre-Lopez, B., de Gomez-Puyou, M. T., Perez-Montfort, R., Costas, M., Gomez-Puyou, A., Torres-Larios, A. Structural basis of human triosephosphate isomerase deficiency: mutation E104D is related to alterations of a conserved water network at the dimer interface. J. Biol. Chem. 283: 23254-23263, 2008. - - - -

Text-mined citations for rs121964845...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 27, 2021