ClinVar Genomic variation as it relates to human health
NM_000492.4(CFTR):c.234dup (p.Trp79fs)
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_000492.4(CFTR):c.234dup (p.Trp79fs)
Variation ID: 928495 Accession: VCV000928495.9
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 7q31.2 7: 117509102-117509103 (GRCh38) [ NCBI UCSC ] 7: 117149156-117149157 (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 Jun 22, 2020 Oct 8, 2024 Nov 23, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000492.4:c.234dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000483.3:p.Trp79fs frameshift NM_000492.3:c.234dupC NC_000007.14:g.117509103dup NC_000007.13:g.117149157dup NG_016465.4:g.48320dup NG_062452.1:g.741dup LRG_663:g.48320dup LRG_663t1:c.234dup - Protein change
- W79fs
- Other names
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- Canonical SPDI
- NC_000007.14:117509102:C:CC
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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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The Genome Aggregation Database (gnomAD) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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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CFTR | - | - |
GRCh38 GRCh37 |
3826 | 5201 |
Conditions - Germline
Condition
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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 (3) |
criteria provided, multiple submitters, no conflicts
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May 22, 2023 | RCV001192431.6 | |
CFTR-related disorder
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Pathogenic/Likely pathogenic (2) |
no assertion criteria provided
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Jun 18, 2024 | RCV001833737.2 |
Pathogenic (1) |
criteria provided, single submitter
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Nov 23, 2023 | RCV004570403.1 |
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
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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
(Sep 28, 2021)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: unknown
Allele origin:
germline
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Johns Hopkins Genomics, Johns Hopkins University
Accession: SCV002051810.1
First in ClinVar: Jan 08, 2022 Last updated: Jan 08, 2022 |
Comment:
CFTR c.234dupC has been reported in an individual with features of cystic fibrosis. This variant (rs751305135) is rare (<0.1%) in a large population dataset (gnomAD: … (more)
CFTR c.234dupC has been reported in an individual with features of cystic fibrosis. This variant (rs751305135) is rare (<0.1%) in a large population dataset (gnomAD: 2/251016 total alleles; 0.0008%; no homozygotes) and has been reported in ClinVar (variant ID: 928495). This frameshift variant results in a premature stop codon in exon 4 likely leading to nonsense-mediated decay and lack of protein production. We consider this variant to be pathogenic. (less)
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Pathogenic
(May 22, 2023)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001360545.3
First in ClinVar: Jun 22, 2020 Last updated: Jun 24, 2023 |
Comment:
Variant summary: CFTR c.234dupC (p.Trp79LeufsX32) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: CFTR c.234dupC (p.Trp79LeufsX32) 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. Variants downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 8e-06 in 251016 control chromosomes (gnomAD). c.234dupC has been reported in the literature in at-least one individual affected with Cystic Fibrosis (example, Schrijver_2016) although a different variant, c.234dupT, also translating to the same protein effect has been reported in affected individuals (example, Petrova_2019, Soe_2017). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 26708955, 30548586, 28174639). Three ClinVar submitters (evaluation after 2014) cite this variant as pathogenic (n=2) and likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Nov 04, 2021)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002732668.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.234dupC pathogenic mutation, located in coding exon 3 of the CFTR gene, results from a duplication of C at nucleotide position 234, causing a … (more)
The c.234dupC pathogenic mutation, located in coding exon 3 of the CFTR gene, results from a duplication of C at nucleotide position 234, causing a translational frameshift with a predicted alternate stop codon (p.W79Lfs*32). This alteration has been detected in individuals with cystic fibrosis or CFTR-related disorders (Schrijver I et al. J Mol Diagn, 2016 Jan;18:39-50). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(Nov 23, 2023)
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criteria provided, single submitter
Method: clinical testing
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Bronchiectasis with or without elevated sweat chloride 1
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV005057472.1
First in ClinVar: Jun 17, 2024 Last updated: Jun 17, 2024 |
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Likely pathogenic
(Oct 19, 2020)
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no assertion criteria provided
Method: clinical testing
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CFTR-related disorders
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002080092.1
First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022 |
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Pathogenic
(Jun 18, 2024)
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no assertion criteria provided
Method: clinical testing
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CFTR-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV005361329.1
First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024 |
Comment:
The CFTR c.234dupC variant is predicted to result in a frameshift and premature protein termination (p.Trp79Leufs*32). This variant has been reported in at least two … (more)
The CFTR c.234dupC variant is predicted to result in a frameshift and premature protein termination (p.Trp79Leufs*32). This variant has been reported in at least two individuals with cystic fibrosis (Schrijver et al. 2016. PubMed ID: 26708955). This variant is reported in 0.012% of alleles in individuals of African descent in gnomAD. Of note, a different single-nucleotide duplication (c.233dupT) leading to the same p.Trp79Leufs*32 frameshift has been reported in the homozygous and compound heterozygous states in individuals with cystic fibrosis (Soe and Gregoire-Bottex 2017. PubMed ID: 28174639; Petrova et al. 2019. PubMed ID: 30548586). Frameshift variants in CFTR are expected to be pathogenic. In summary, the c.234dupC variant is interpreted as pathogenic. (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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Comprehensive genotyping reveals novel CFTR variants in cystic fibrosis patients from the Russian Federation. | Petrova NV | Clinical genetics | 2019 | PMID: 30548586 |
A rare CFTR mutation associated with severe disease progression in a 10-year-old Hispanic patient. | Soe K | Clinical case reports | 2017 | PMID: 28174639 |
The Spectrum of CFTR Variants in Nonwhite Cystic Fibrosis Patients: Implications for Molecular Diagnostic Testing. | Schrijver I | The Journal of molecular diagnostics : JMD | 2016 | PMID: 26708955 |
Text-mined citations for rs1189377616 ...
HelpRecord last updated Oct 13, 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.