ClinVar Genomic variation as it relates to human health
NM_000203.5(IDUA):c.1743C>G (p.Tyr581Ter)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000203.5(IDUA):c.1743C>G (p.Tyr581Ter)
Variation ID: 550883 Accession: VCV000550883.14
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 4p16.3 4: 1004027 (GRCh38) [ NCBI UCSC ] 4: 997815 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Aug 5, 2018 Feb 14, 2024 Jun 28, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000203.5:c.1743C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000194.2:p.Tyr581Ter nonsense NM_001363576.1:c.1347C>G NP_001350505.1:p.Tyr449Ter nonsense NR_110313.1:n.1835C>G non-coding transcript variant NC_000004.12:g.1004027C>G NC_000004.11:g.997815C>G NG_008103.1:g.22031C>G LRG_1277:g.22031C>G LRG_1277t1:c.1743C>G LRG_1277p1:p.Tyr581Ter - Protein change
- Y581*, Y449*
- Other names
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- Canonical SPDI
- NC_000004.12:1004026:C:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00002
- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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IDUA | - | - |
GRCh38 GRCh37 |
1392 | 2157 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (1) |
criteria provided, single submitter
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Feb 27, 2017 | RCV000665761.1 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jun 28, 2023 | RCV001214746.9 | |
Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jun 7, 2021 | RCV001662734.6 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Feb 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Hurler syndrome
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000789930.1
First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018 |
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Likely pathogenic
(Apr 07, 2021)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001873975.1
First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021 |
Comment:
Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 73 amino acids are lost, and other loss-of-function variants have been … (more)
Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 73 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 21394825, 27196898, 9672523, 21521498, 21639919, 32432561, 33072983, 33147872, 30442156, 25525159) (less)
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Pathogenic
(Nov 11, 2021)
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criteria provided, single submitter
Method: clinical testing
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Mucopolysaccharidosis type 1
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002041506.1
First in ClinVar: Dec 25, 2021 Last updated: Dec 25, 2021 |
Comment:
Variant summary: IDUA c.1743C>G (p.Tyr581X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: IDUA c.1743C>G (p.Tyr581X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 1.6e-05 in 251162 control chromosomes (gnomAD). c.1743C>G has been reported in the literature in individuals affected with Mucopolysaccharidosis Type 1 (e.g. Souillet_2003, Chkioua_2011, Tebani_2016, Guffon_2021). These data indicate that the variant is likely to be associated with disease. Three ClinVar submitters (evaluation after 2014) cite the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Jun 07, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002023109.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Jun 28, 2023)
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criteria provided, single submitter
Method: clinical testing
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Mucopolysaccharidosis type 1
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001386447.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Tyr581*) in the IDUA gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Tyr581*) in the IDUA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in IDUA are known to be pathogenic (PMID: 11735025, 21480867). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 550883). This premature translational stop signal has been observed in individual(s) with mucopolysaccharidosis type I (PMID: 21394825, 27196898). This variant is present in population databases (rs776787370, gnomAD 0.02%). (less)
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Germline Functional Evidence
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 germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Long term disease burden post-transplantation: three decades of observations in 25 Hurler patients successfully treated with hematopoietic stem cell transplantation (HSCT). | Guffon N | Orphanet journal of rare diseases | 2021 | PMID: 33517895 |
Newborn screening in mucopolysaccharidoses. | Donati MA | Italian journal of pediatrics | 2018 | PMID: 30442156 |
Newborn screening for lysosomal storage disorders by tandem mass spectrometry in North East Italy. | Burlina AB | Journal of inherited metabolic disease | 2018 | PMID: 29143201 |
Clinical and Molecular Characterization of Patients with Mucopolysaccharidosis Type I in an Algerian Series. | Tebani A | International journal of molecular sciences | 2016 | PMID: 27196898 |
Mucopolysaccharidosis I mutations in Chinese patients: identification of 27 novel mutations and 6 cases involving prenatal diagnosis. | Wang X | Clinical genetics | 2012 | PMID: 21480867 |
Hurler disease (mucopolysaccharidosis type IH): clinical features and consanguinity in Tunisian population. | Chkioua L | Diagnostic pathology | 2011 | PMID: 22074387 |
IDUA mutational profiling of a cohort of 102 European patients with mucopolysaccharidosis type I: identification and characterization of 35 novel α-L-iduronidase (IDUA) alleles. | Bertola F | Human mutation | 2011 | PMID: 21394825 |
Outcome of 27 patients with Hurler's syndrome transplanted from either related or unrelated haematopoietic stem cell sources. | Souillet G | Bone marrow transplantation | 2003 | PMID: 12796790 |
Mutational analysis of 85 mucopolysaccharidosis type I families: frequency of known mutations, identification of 17 novel mutations and in vitro expression of missense mutations. | Beesley CE | Human genetics | 2001 | PMID: 11735025 |
Text-mined citations for rs776787370 ...
HelpRecord last updated Sep 29, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.