This variant causes an in-frame deletion of one amino acid (glutamic acid) at codon 273 of the OTC protein. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in multiple male and female individuals affected with late-onset ornithine transcarbamylase deficiency (PMID: 8956045, 10799432, 17334707, 25433810, 34014557, 35145162). This variant has also been observed de novo in a 1.5 month-old female affected with ornithine transcarbamylase deficiency (PMID: 17334707). This variant has been identified in 1/183136 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic.
ClinVar Genomic variation as it relates to human health
NM_000531.6(OTC):c.814GAG[1] (p.Glu273del)
Germline
Classification
Help
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.
(6)
Help
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.
Pathogenic/Likely pathogenic
6
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000531.6(OTC):c.814GAG[1] (p.Glu273del)
Variation ID: 97337 Accession: VCV000097337.13
- Type and length
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Microsatellite, 3 bp
- Location
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Cytogenetic: Xp11.4 X: 38408972-38408974 (GRCh38) [ NCBI UCSC ] X: 38268225-38268227 (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 Feb 20, 2014 Jun 29, 2024 Mar 5, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000531.6:c.814GAG[1] MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000522.3:p.Glu273del inframe deletion NM_000531.6:c.817_819del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_000531.6:c.817_819delGAG MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_000531.5:c.817_819del NC_000023.11:g.38408972GAG[1] NC_000023.10:g.38268225GAG[1] NG_008471.1:g.61490GAG[1] LRG_846:g.61490GAG[1] LRG_846t1:c.814GAG[1] LRG_846p1:p.Glu273del - Protein change
- E273del
- Other names
- -
- Canonical SPDI
- NC_000023.11:38408971:GAGGAG:GAG
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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
Help
The frequency of the allele represented by this VCV record.
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- 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 | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
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. |
|||
| OTC | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
903 | 1056 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
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
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (1) |
no assertion criteria provided
|
- | RCV000083584.1 | |
| Pathogenic/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
|
Mar 5, 2024 | RCV000692945.13 |
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
Help
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
Help
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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|---|---|---|---|---|---|
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Likely pathogenic
(Aug 20, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Ornithine carbamoyltransferase deficiency
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004201313.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
|
|
|
Likely pathogenic
(Sep 06, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Ornithine carbamoyltransferase deficiency
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV004357055.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This variant causes an in-frame deletion of one amino acid (glutamic acid) at codon 273 of the OTC protein. To our knowledge, functional studies have … (more)
This variant causes an in-frame deletion of one amino acid (glutamic acid) at codon 273 of the OTC protein. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in multiple male and female individuals affected with late-onset ornithine transcarbamylase deficiency (PMID: 8956045, 10799432, 17334707, 25433810, 34014557, 35145162). This variant has also been observed de novo in a 1.5 month-old female affected with ornithine transcarbamylase deficiency (PMID: 17334707). This variant has been identified in 1/183136 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic. (less)
|
|
|
Likely Pathogenic
(Jun 26, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Ornithine carbamoyltransferase deficiency
(X-linked inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004829119.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
|
Comment:
This variant causes an in-frame deletion of one amino acid (glutamic acid) at codon 273 of the OTC protein. To our knowledge, functional studies have … (more)
This variant causes an in-frame deletion of one amino acid (glutamic acid) at codon 273 of the OTC protein. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in multiple male and female individuals affected with late-onset ornithine transcarbamylase deficiency (PMID: 8956045, 17334707, 25433810, 34014557, 35145162). This variant has also been observed de novo in a 1.5 month-old female affected with ornithine transcarbamylase deficiency (PMID: 17334707). This variant has been identified in 1/183136 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic. (less)
Number of individuals with the variant: 1
|
|
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Pathogenic
(Mar 05, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Ornithine carbamoyltransferase deficiency
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001360757.5
First in ClinVar: Jun 22, 2020 Last updated: Jun 29, 2024 |
Comment:
Variant summary: OTC c.817_819delGAG (p.Glu273del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele … (more)
Variant summary: OTC c.817_819delGAG (p.Glu273del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele was found at a frequency of 5.5e-06 in 183136 control chromosomes (gnomAD). c.817_819delGAG has been reported in the literature in multiple individuals affected with Ornithine Transcarbamylase Deficiency (Segues_1996, Arranz_2007, Martin-Hernandez_2014, Gobin-Limballe_2021, Toquet_2021). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 25433810, 17334707, 8956045, 34014569, 34014557). ClinVar contains an entry for this variant (Variation ID: 97337). Based on the evidence outlined above, the variant was classified as pathogenic. (less)
|
|
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Pathogenic
(Jan 15, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Ornithine carbamoyltransferase deficiency
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000820796.4
First in ClinVar: Oct 10, 2018 Last updated: Feb 14, 2024 |
Comment:
This variant, c.817_819del, results in the deletion of 1 amino acid(s) of the OTC protein (p.Glu273del), but otherwise preserves the integrity of the reading frame. … (more)
This variant, c.817_819del, results in the deletion of 1 amino acid(s) of the OTC protein (p.Glu273del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs72558452, gnomAD 0.001%), including at least one homozygous and/or hemizygous individual. This variant has been observed in individual(s) with ornithine transcarbamylase deficiency (PMID: 8956045, 17334707, 25433810, 32420033, 34014557, 34014569). ClinVar contains an entry for this variant (Variation ID: 97337). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
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pathogenic
(-)
|
no assertion criteria provided
Method: not provided
|
not provided
Affected status: not provided
Allele origin:
unknown
|
GenMed Metabolism Lab
Accession: SCV000115670.1
First in ClinVar: Feb 20, 2014 Last updated: Feb 20, 2014
Comment:
p.Glu273del, Late
|
Comment:
Converted during submission to Pathogenic.
|
Comment:
Comment:
This variant causes an in-frame deletion of one amino acid (glutamic acid) at codon 273 of the OTC protein. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in multiple male and female individuals affected with late-onset ornithine transcarbamylase deficiency (PMID: 8956045, 17334707, 25433810, 34014557, 35145162). This variant has also been observed de novo in a 1.5 month-old female affected with ornithine transcarbamylase deficiency (PMID: 17334707). This variant has been identified in 1/183136 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic.
Comment:
Variant summary: OTC c.817_819delGAG (p.Glu273del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele was found at a frequency of 5.5e-06 in 183136 control chromosomes (gnomAD). c.817_819delGAG has been reported in the literature in multiple individuals affected with Ornithine Transcarbamylase Deficiency (Segues_1996, Arranz_2007, Martin-Hernandez_2014, Gobin-Limballe_2021, Toquet_2021). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 25433810, 17334707, 8956045, 34014569, 34014557). ClinVar contains an entry for this variant (Variation ID: 97337). Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
This variant, c.817_819del, results in the deletion of 1 amino acid(s) of the OTC protein (p.Glu273del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs72558452, gnomAD 0.001%), including at least one homozygous and/or hemizygous individual. This variant has been observed in individual(s) with ornithine transcarbamylase deficiency (PMID: 8956045, 17334707, 25433810, 32420033, 34014557, 34014569). ClinVar contains an entry for this variant (Variation ID: 97337). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. For these reasons, this variant has been classified as Pathogenic.
Comment:
Converted during submission to Pathogenic.
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. |
Comment:
This variant causes an in-frame deletion of one amino acid (glutamic acid) at codon 273 of the OTC protein. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in multiple male and female individuals affected with late-onset ornithine transcarbamylase deficiency (PMID: 8956045, 10799432, 17334707, 25433810, 34014557, 35145162). This variant has also been observed de novo in a 1.5 month-old female affected with ornithine transcarbamylase deficiency (PMID: 17334707). This variant has been identified in 1/183136 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic.
Comment:
This variant causes an in-frame deletion of one amino acid (glutamic acid) at codon 273 of the OTC protein. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in multiple male and female individuals affected with late-onset ornithine transcarbamylase deficiency (PMID: 8956045, 17334707, 25433810, 34014557, 35145162). This variant has also been observed de novo in a 1.5 month-old female affected with ornithine transcarbamylase deficiency (PMID: 17334707). This variant has been identified in 1/183136 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic.
Comment:
Variant summary: OTC c.817_819delGAG (p.Glu273del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele was found at a frequency of 5.5e-06 in 183136 control chromosomes (gnomAD). c.817_819delGAG has been reported in the literature in multiple individuals affected with Ornithine Transcarbamylase Deficiency (Segues_1996, Arranz_2007, Martin-Hernandez_2014, Gobin-Limballe_2021, Toquet_2021). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 25433810, 17334707, 8956045, 34014569, 34014557). ClinVar contains an entry for this variant (Variation ID: 97337). Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
This variant, c.817_819del, results in the deletion of 1 amino acid(s) of the OTC protein (p.Glu273del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs72558452, gnomAD 0.001%), including at least one homozygous and/or hemizygous individual. This variant has been observed in individual(s) with ornithine transcarbamylase deficiency (PMID: 8956045, 17334707, 25433810, 32420033, 34014557, 34014569). ClinVar contains an entry for this variant (Variation ID: 97337). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. For these reasons, this variant has been classified as Pathogenic.
Comment:
Converted during submission to Pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Derivation of healthy hepatocyte-like cells from a female patient with ornithine transcarbamylase deficiency through X-inactivation selection. | Santamaria R | Scientific reports | 2022 | PMID: 35145162 |
| OTC deficiency in females: Phenotype-genotype correlation based on a 130-family cohort. | Gobin-Limballe S | Journal of inherited metabolic disease | 2021 | PMID: 34014569 |
| Adult-onset diagnosis of urea cycle disorders: Results of a French cohort of 71 patients. | Toquet S | Journal of inherited metabolic disease | 2021 | PMID: 34014557 |
| The E273del variant of uncertain significance of the ornithine transcarbamylase gene - a case for reclassification. | Ducich N | Molecular genetics and metabolism reports | 2020 | PMID: 32420033 |
| Urea cycle disorders in Spain: an observational, cross-sectional and multicentric study of 104 cases. | Martín-Hernández E | Orphanet journal of rare diseases | 2014 | PMID: 25433810 |
| Estimation of the total number of disease-causing mutations in ornithine transcarbamylase (OTC) deficiency. Value of the OTC structure in predicting a mutation pathogenic potential. | Arranz JA | Journal of inherited metabolic disease | 2007 | PMID: 17334707 |
| Under recognition of late onset ornithine transcarbamylase deficiency. | Schultz RE | Archives of disease in childhood | 2000 | PMID: 10799432 |
| A 3-base pair in-frame deletion in exon 8 (delGlu272/273) of the ornithine transcarbamylase gene in late-onset hyperammonemic coma. | Ségues B | Human mutation | 1996 | PMID: 8956045 |
Text-mined citations for rs72558452 ...
HelpThese 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 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.