Variant summary: CFTR c.2668C>T (p.Gln890X) 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 was absent in 251194 control chromosomes. c.2668C>T has been reported in the literature in multiple individuals affected with Cystic Fibrosis (example, Tsui_1992, Ghanem_1994, Sosnay_2013). These data indicate that the variant is very likely to be associated with disease. Three clinical diagnostic laboratories and one expert panel (CFTR2) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
ClinVar Genomic variation as it relates to human health
NM_000492.4(CFTR):c.2668C>T (p.Gln890Ter)
Germline
Reviewed by expert panel
Help
Reviewed by expert panel. Learn more about how ClinVar calculates review status.
Pathogenic
for
Cystic fibrosis
Classification is based on the expert panel submission
Mar 2017 by
CFTR2
Help
The classification is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000492.4(CFTR):c.2668C>T (p.Gln890Ter)
Variation ID: 7204 Accession: VCV000007204.23
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 7q31.2 7: 117603542 (GRCh38) [ NCBI UCSC ] 7: 117243596 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Oct 11, 2015 Jun 29, 2025 Mar 17, 2017 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000492.4:c.2668C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000483.3:p.Gln890Ter nonsense NC_000007.14:g.117603542C>T NC_000007.13:g.117243596C>T NG_016465.4:g.142759C>T LRG_663:g.142759C>T LRG_663t1:c.2668C>T LRG_663p1:p.Gln890Ter - Protein change
- Q890*
- Other names
- -
- Canonical SPDI
- NC_000007.14:117603541:C:T
-
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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Trans-Omics for Precision Medicine (TOPMed) 0.00000
The Genome Aggregation Database (gnomAD) 0.00003
The Genome Aggregation Database (gnomAD), exomes 0.00000
- 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. |
|||
| CFTR | Gene associated with autosomal recessive phenotype | Not yet evaluated |
GRCh38 GRCh37 |
3753 | 6142 | |
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 (8) |
reviewed by expert panel
|
Mar 17, 2017 | RCV000007625.20 | |
| Pathogenic (3) |
criteria provided, single submitter
|
Jun 7, 2017 | RCV000505859.6 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Feb 16, 2023 | RCV003473044.1 | |
| Pathogenic (1) |
no assertion criteria provided
|
Mar 17, 2017 | RCV001831549.1 | |
| Pathogenic (1) |
criteria provided, single submitter
|
May 24, 2024 | RCV005042007.1 |
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
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. |
Expand all rows
Collapse all rows
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. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Mar 17, 2017)
C
Contributing to aggregate classification
|
reviewed by expert panel
|
Cystic fibrosis |
CFTR2
Study: CFTR2
Accession: SCV000071548.4 First in ClinVar: Oct 18, 2013 Last updated: Jan 06, 2018 |
Observation: 1
Collection method: research
Allele origin: germline
Affected status: yes
Observation 1
Collection method: research
Allele origin: germline
Affected status: yes
|
|
|
Pathogenic
(Jan 29, 2018)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
cystic fibrosis |
CFTR-France
Accession: SCV001169522.1
First in ClinVar: Mar 16, 2020 Last updated: Mar 16, 2020 |
Observation: 1
Collection method: curation
Allele origin: germline
Affected status: yes
Observation 1
Collection method: curation
Allele origin: germline
Affected status: yes
|
|
|
Pathogenic
(Feb 22, 2021)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
Cystic fibrosis |
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001482256.1
First in ClinVar: Mar 07, 2021 Last updated: Mar 07, 2021 |
Comment:
show
Variant summary: CFTR c.2668C>T (p.Gln890X) 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 was absent in 251194 control chromosomes. c.2668C>T has been reported in the literature in multiple individuals affected with Cystic Fibrosis (example, Tsui_1992, Ghanem_1994, Sosnay_2013). These data indicate that the variant is very likely to be associated with disease. Three clinical diagnostic laboratories and one expert panel (CFTR2) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
|
Pathogenic
(Aug 23, 2021)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
Cystic fibrosis |
Johns Hopkins Genomics, Johns Hopkins University
Accession: SCV001905481.1
First in ClinVar: Sep 23, 2021 Last updated: Sep 23, 2021 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
|
Pathogenic
(Jun 07, 2017)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
not provided |
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000601077.2
First in ClinVar: Sep 30, 2017 Last updated: Jan 01, 2022 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
|
Pathogenic
(Feb 06, 2015)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
Cystic fibrosis |
Ambry Genetics
Accession: SCV002743851.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
show
The p.Q890* pathogenic mutation (also known as c.2668C>T), located in coding exon 17 of the CFTR gene, results from a C to T substitution at nucleotide position 2668. This changes the amino acid from a glutamine to a stop codon within coding exon 17. This mutation was originally detected in two individuals in a Portuguese family with classic CF and nasal polyposis, both with deltaF508 on the other chromosome and one noted to have an elevated sweat chloride of 140 mmol/L (Ghanem N et al. Genomics. 1994;21(2):434-436). In addition to the clinical data presented in the literature, since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
|
Pathogenic
(May 24, 2024)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
Hereditary pancreatitis
Bronchiectasis with or without elevated sweat chloride 1 Cystic fibrosis Congenital bilateral aplasia of vas deferens from CFTR mutation
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. |
Fulgent Genetics, Fulgent Genetics
Accession: SCV005673368.1
First in ClinVar: Jan 25, 2025 Last updated: Jan 25, 2025 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
|
Pathogenic
(Dec 16, 2024)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
Cystic fibrosis |
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002165083.4
First in ClinVar: Mar 28, 2022 Last updated: Feb 25, 2025 |
Comment:
show
This sequence change creates a premature translational stop signal (p.Gln890*) in the CFTR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of cystic fibrosis (PMID: 7522211). ClinVar contains an entry for this variant (Variation ID: 7204). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
|
Pathogenic
(Feb 16, 2023)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
Bronchiectasis with or without elevated sweat chloride 1 |
Baylor Genetics
Accession: SCV004213563.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
Observation: 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
|
|
|
Pathogenic
(May 15, 1994)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
CYSTIC FIBROSIS |
OMIM
Accession: SCV000027826.2
First in ClinVar: Apr 04, 2013 Last updated: Apr 12, 2018 |
Observation: 1
Collection method: literature only
Allele origin: germline
Affected status: not provided
Observation 1
Collection method: literature only
Allele origin: germline
Affected status: not provided
Comment on evidence:
In 2 related Portuguese patients with cystic fibrosis (CF; 219700), Ghanem et al. (1994) identified a C-to-T substitution at nucleotide 2880 in exon 15, resulting … (more)
In 2 related Portuguese patients with cystic fibrosis (CF; 219700), Ghanem et al. (1994) identified a C-to-T substitution at nucleotide 2880 in exon 15, resulting in a stop codon at position 890. This mutation was found in a 13-year-old girl and her 15-year-old uncle, who have a classic form of the disease and nasal polyposis. Both patients had F508del on the other CF chromosome, and the uncle had a positive sweat test (140 mmol per liter). The mutation changed the restriction sites MseI(+) and MboII(-). (less)
|
|
|
Pathogenic
(-)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
not provided |
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001742476.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
|
|
|
Pathogenic
(-)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
not provided |
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001954821.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
|
|
|
Pathogenic
(Mar 17, 2017)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
CFTR-related disorders |
Natera, Inc.
Accession: SCV002080789.1
First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
|
Pathogenic
(Feb 03, 2016)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
Cystic fibrosis |
Counsyl
Accession: SCV000485207.3
First in ClinVar: Oct 11, 2015 Last updated: Jun 29, 2025 |
Comment:
show
This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. (less)
Observation: 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
|
|
Comment:
Comment:
Disease-causing CFTR variant. See www.CFTR2.org for phenotype information.
Comment:
The p.Q890* pathogenic mutation (also known as c.2668C>T), located in coding exon 17 of the CFTR gene, results from a C to T substitution at nucleotide position 2668. This changes the amino acid from a glutamine to a stop codon within coding exon 17. This mutation was originally detected in two individuals in a Portuguese family with classic CF and nasal polyposis, both with deltaF508 on the other chromosome and one noted to have an elevated sweat chloride of 140 mmol/L (Ghanem N et al. Genomics. 1994;21(2):434-436). In addition to the clinical data presented in the literature, since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
Comment:
This sequence change creates a premature translational stop signal (p.Gln890*) in the CFTR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of cystic fibrosis (PMID: 7522211). ClinVar contains an entry for this variant (Variation ID: 7204). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Comment:
This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. | Sosnay PR | Nature genetics | 2013 | PMID: 23974870 |
| An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: results from an ethnically diverse clinical sample of 23,453 individuals. | Lazarin GA | Genetics in medicine : official journal of the American College of Medical Genetics | 2013 | PMID: 22975760 |
| Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice. | Castellani C | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society | 2008 | PMID: 18456578 |
| Relation between mutations of the cystic fibrosis gene and idiopathic pancreatitis. | Cohn JA | The New England journal of medicine | 1998 | PMID: 9725922 |
| Identification of eight mutations and three sequence variations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. | Ghanem N | Genomics | 1994 | PMID: 7522211 |
| Molecular basis of defective anion transport in L cells expressing recombinant forms of CFTR. | Yang Y | Human molecular genetics | 1993 | PMID: 7691345 |
| Mutations and sequence variations detected in the cystic fibrosis transmembrane conductance regulator (CFTR) gene: a report from the Cystic Fibrosis Genetic Analysis Consortium. | Tsui LC | Human mutation | 1992 | PMID: 1284534 |
| A cluster of cystic fibrosis mutations in the first nucleotide-binding fold of the cystic fibrosis conductance regulator protein. | Cutting GR | Nature | 1990 | PMID: 1695717 |
| https://cftr2.org | - | - | - | - |
Text-mined citations for rs79633941 ...
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 Jun 29, 2025
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.