ClinVar Genomic variation as it relates to human health
NM_000111.3(SLC26A3):c.2024_2026dup (p.Ile675dup)
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_000111.3(SLC26A3):c.2024_2026dup (p.Ile675dup)
Variation ID: 55988 Accession: VCV000055988.10
- Type and length
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Duplication, 3 bp
- Location
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Cytogenetic: 7q22.3 7: 107772089-107772090 (GRCh38) [ NCBI UCSC ] 7: 107412534-107412535 (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 Apr 4, 2013 Feb 14, 2024 Jan 26, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000111.3:c.2024_2026dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000102.1:p.Ile675dup inframe insertion NM_000111.2:c.2024_2026dupTCA NC_000007.14:g.107772091_107772093dup NC_000007.13:g.107412536_107412538dup NG_008046.1:g.36142_36144dup LRG_683:g.36142_36144dup - Protein change
- Other names
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- Canonical SPDI
- NC_000007.14:107772089:TGAT:TGATGAT
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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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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
Help
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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SLC26A3 | - | - |
GRCh38 GRCh37 |
747 | 773 |
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
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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 (4) |
criteria provided, multiple submitters, no conflicts
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Mar 18, 2020 | RCV000049397.9 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jan 26, 2024 | RCV001682751.4 |
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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Pathogenic
(Jan 26, 2024)
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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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Invitae
Accession: SCV002141114.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
This variant, c.2024_2026dup, results in the insertion of 1 amino acid(s) of the SLC26A3 protein (p.Ile675dup), but otherwise preserves the integrity of the reading frame. … (more)
This variant, c.2024_2026dup, results in the insertion of 1 amino acid(s) of the SLC26A3 protein (p.Ile675dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs386833470, gnomAD 0.01%). This variant has been observed in individuals with congenital chloride diarrhea (PMID: 9718329, 18216024, 21332001, 28644346). This variant is also known as I675/6ins, c.2025_2026insATC, and I668–669ins. ClinVar contains an entry for this variant (Variation ID: 55988). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects SLC26A3 function (PMID: 12411484, 18216024). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Congenital secretory diarrhea, chloride type
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001137438.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Pathogenic
(Mar 18, 2020)
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criteria provided, single submitter
Method: clinical testing
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Congenital secretory diarrhea, chloride type
Affected status: yes
Allele origin:
unknown
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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001369909.2
First in ClinVar: Jul 04, 2020 Last updated: Dec 12, 2020 |
Comment:
This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PS3,PS4,PM2,PM3,PM4. This variant was detected in homozygous state.
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Pathogenic
(Sep 15, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001905515.1
First in ClinVar: Sep 25, 2021 Last updated: Sep 25, 2021 |
Clinical Features:
Diarrhea (present)
Sex: female
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probable-pathogenic
(-)
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no assertion criteria provided
Method: not provided
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Congenital secretory diarrhea, chloride type
Affected status: not provided
Allele origin:
not provided
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Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)
Accession: SCV000081830.1
First in ClinVar: Jul 24, 2013 Last updated: Jul 24, 2013
Comment:
FinDis database variant: This variant was not found or characterized by our laboratory, data were collected from public sources: see reference
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Comment:
Converted during submission to Likely pathogenic.
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Pathogenic
(Mar 28, 2008)
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no assertion criteria provided
Method: literature only
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DIARRHEA 1, SECRETORY CHLORIDE, CONGENITAL
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000038522.2
First in ClinVar: Apr 04, 2013 Last updated: Oct 23, 2020 |
Comment on evidence:
Hoglund et al. (1998) described an in-frame addition of an ATC (ile) in exon 18 of the SLC26A3 gene, constituting codon 676, in 12 Polish … (more)
Hoglund et al. (1998) described an in-frame addition of an ATC (ile) in exon 18 of the SLC26A3 gene, constituting codon 676, in 12 Polish cases of congenital chloride diarrhea (DIAR1; 214700) and constituting the 'Polish founder mutation.' Dorwart et al. (2008) showed that the ile676 insertion results in the misfolding of the STAS domain of SLC26A3. Mutant SLC26A3 accumulated in the endoplasmic reticulum rather being transported to the plasma membrane, and it was rapidly degraded. (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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Twelve Novel Mutations in the SLC26A3 Gene in 17 Sporadic Cases of Congenital Chloride Diarrhea. | Amato F | Journal of pediatric gastroenterology and nutrition | 2017 | PMID: 28644346 |
A Turkish case of congenital chloride diarrhea with SLC26A3 gene (c.2025_2026insATC) mutation: diagnostic pitfalls. | Özbay Hoşnut F | The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology | 2010 | PMID: 21332001 |
Congenital chloride-losing diarrhea causing mutations in the STAS domain result in misfolding and mistrafficking of SLC26A3. | Dorwart MR | The Journal of biological chemistry | 2008 | PMID: 18216024 |
A molecular mechanism for aberrant CFTR-dependent HCO(3)(-) transport in cystic fibrosis. | Ko SB | The EMBO journal | 2002 | PMID: 12411484 |
Genetic background of congenital chloride diarrhea in high-incidence populations: Finland, Poland, and Saudi Arabia and Kuwait. | Höglund P | American journal of human genetics | 1998 | PMID: 9718329 |
Text-mined citations for rs121913031 ...
HelpRecord last updated Feb 20, 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.