VCV000007129.143 - ClinVar

NM_000492.4(CFTR):c.3846G>A (p.Trp1282Ter)

Germline

Top reviewed classifications are shown here.

Submission summary:

36 submissions

33 submitters

8 conditions

Practice guidelines

Pathogenic

Mar 2004 by American Colle…

for Cystic fibrosis

Reviewed by expert panel

Pathogenic

Mar 2017 by CFTR2

for Cystic fibrosis

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

This variant is part of a Haplotype

NM_000492.4(CFTR):c.[3846G>A;3848G>T]

Identifiers

NM_000492.4(CFTR):c.3846G>A (p.Trp1282Ter)

Variation ID: 7129 Accession: VCV000007129.143

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 7q31.2 7: 117642566 (GRCh38) [ NCBI UCSC ] 7: 117282620 (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	Apr 8, 2015	Oct 20, 2024	Mar 3, 2004

HGVS

Nucleotide	Protein	Molecular consequence
NM_000492.4:c.3846G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000483.3:p.Trp1282Ter	nonsense
NC_000007.14:g.117642566G>A
NC_000007.13:g.117282620G>A
NG_016465.4:g.181783G>A
LRG_663:g.181783G>A
LRG_663t1:c.3846G>A	LRG_663p1:p.Trp1282Ter

... more HGVS ... less HGVS

Protein change

W1282*

Other names

Canonical SPDI

NC_000007.14:117642565:G:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

The Genome Aggregation Database (gnomAD) 0.00019

Trans-Omics for Precision Medicine (TOPMed) 0.00025

Links

ClinGen: CA340638 Genetic Testing Registry (GTR): GTR000074114 Genetic Testing Registry (GTR): GTR000257096 Genetic Testing Registry (GTR): GTR000500233 Genetic Testing Registry (GTR): GTR000576392 OMIM: 602421.0022 dbSNP: rs77010898 VarSome

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
Gene	OMIM	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		-	-	GRCh38 GRCh37	3825	5200

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.
Cystic fibrosis	Pathogenic (17)	practice guideline	Mar 3, 2004	RCV000007549.51
not provided	Pathogenic (11)	criteria provided, multiple submitters, no conflicts	Dec 8, 2023	RCV000271658.49
not specified	Pathogenic (1)	criteria provided, single submitter	Sep 5, 2017	RCV000780159.9
Bronchiectasis with or without elevated sweat chloride 1 Congenital bilateral aplasia of vas deferens from CFTR mutation Cystic fibrosis Hereditary pancreatitis	Pathogenic (1)	criteria provided, single submitter	Oct 31, 2018	RCV000763161.10
Congenital bilateral aplasia of vas deferens from CFTR mutation Cystic fibrosis	Pathogenic (2)	criteria provided, single submitter	-	RCV001004509.11
CFTR-related disorder	Pathogenic (2)	no assertion criteria provided	Jul 3, 2024	RCV002228015.12
Hereditary pancreatitis	Pathogenic (1)	criteria provided, single submitter	May 12, 2021	RCV002255994.9
Bronchiectasis with or without elevated sweat chloride 1	Pathogenic (1)	criteria provided, single submitter	Mar 29, 2024	RCV003473013.2

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.
pathogenic (Mar 03, 2004)	practice guideline (Guideline for cystic fibrosis carrier screening) Method: curation	Cystic fibrosis (Autosomal recessive inheritance) Affected status: unknown Allele origin: germline	American College of Medical Genetics and Genomics (ACMG) Study: The ACMG recommended carrier screening panel Accession: SCV000071407.2 First in ClinVar: Jun 04, 2013 Last updated: Apr 08, 2015	Publications: PubMed (1) PubMed: 11280952 pmc: 3110945 pmc: 3110945 Comment: Converted during submission to Pathogenic.
Pathogenic (Mar 17, 2017)	reviewed by expert panel (Sosnay PR et al. (Nat Genet 2013)) Method: research	Cystic fibrosis Affected status: yes Allele origin: germline	CFTR2 Study: CFTR2 Accession: SCV000071562.4 First in ClinVar: Oct 18, 2013 Last updated: Dec 26, 2017	Other databases https://cftr2.org https://cftr2.org
Pathogenic (Dec 15, 2014)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	Cystic Fibrosis (Autosomal recessive inheritance) Affected status: not provided Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Study: CSER-MedSeq Accession: SCV000221178.2 First in ClinVar: Apr 08, 2015 Last updated: Jun 29, 2015	Publications: PubMed (4) PubMed: 2210768‚ 2236053‚ 1721624‚ 1370365 Comment: The Trp1282X variant in CFTR has been identified in numerous patients with cystic fibrosis (Viduad 1990, Kerem 1990, Hamosh 1991, Shoshani 1992). This variant is … (more) The Trp1282X variant in CFTR has been identified in numerous patients with cystic fibrosis (Viduad 1990, Kerem 1990, Hamosh 1991, Shoshani 1992). This variant is present on the American Board of Medical Genetics CFTR mutation panel (http://www.acmg.net/Pages/ACMG_Activities/stds-2002/cf.htm). This nonsense variant leads to a premature termination codon at position 1282, which is predicted to lead to a truncated or absent protein. In summary, this variant meets our criteria for pathogenicity. (less) Number of individuals with the variant: 2
Pathogenic (Jan 25, 2018)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000330916.4 First in ClinVar: Dec 06, 2016 Last updated: Dec 15, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CFTR http://www.cftr2.org/ http://www.cftr2.org/ http://www.ncbi.nlm.nih.gov/site… http://www.ncbi.nlm.nih.gov/sites/GeneTests/review/gene/CFTR Number of individuals with the variant: 7 Sex: mixed
Pathogenic (Sep 05, 2017)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV000917207.1 First in ClinVar: Jun 03, 2019 Last updated: Jun 03, 2019	Publications: PubMed (3) PubMed: 12767731‚ 27707539‚ 23974870 Comment: Variant summary: The CFTR c.3846G>A (p.Trp1282X) variant results in a premature termination codon, predicted to cause a truncated or absent CFTR protein due to nonsense … (more) Variant summary: The CFTR c.3846G>A (p.Trp1282X) variant results in a premature termination codon, predicted to cause a truncated or absent CFTR protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant was found in 46/120654 control chromosomes at a frequency of 0.0003813, which does not exceed the estimated maximal expected allele frequency of a pathogenic CFTR variant (0.0129603). The variant is a common disease variant reported in numerous affected individuals in the literature. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic, including CFTR2. Taken together, this variant is classified as pathogenic. (less)
Pathogenic (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Congenital bilateral aplasia of vas deferens from CFTR mutation Cystic fibrosis Affected status: unknown Allele origin: germline	Baylor Genetics Accession: SCV001163554.1 First in ClinVar: Mar 01, 2020 Last updated: Mar 01, 2020
Pathogenic (Jan 29, 2018)	criteria provided, single submitter (Claustres M et al. (Hum Mutat 2017)) Method: curation	cystic fibrosis Affected status: yes Allele origin: germline	CFTR-France Accession: SCV001169345.1 First in ClinVar: Mar 16, 2020 Last updated: Mar 16, 2020	Publications: PubMed (1) PubMed: 28603918
Pathogenic (Oct 18, 2019)	criteria provided, single submitter (Myriad Women's Health Autosomal Recessive and X-Linked Classification Criteria (2019)) Method: clinical testing	Cystic fibrosis Affected status: unknown Allele origin: unknown	Myriad Genetics, Inc. Accession: SCV001194202.2 First in ClinVar: Apr 06, 2020 Last updated: Jul 06, 2020	Publications: PubMed (1) PubMed: 23974870 Comment: NM_000492.3(CFTR):c.3846G>A(W1282) is classified as pathogenic in the context of cystic fibrosis and is associated with the classic form of disease. Sources cited for classification include … (more) NM_000492.3(CFTR):c.3846G>A(W1282) is classified as pathogenic in the context of cystic fibrosis and is associated with the classic form of disease. Sources cited for classification include the following: PMID: 23974870. Classification of NM_000492.3(CFTR):c.3846G>A(W1282) is based on the following criteria: The variant causes a premature termination codon that is expected to be targeted by nonsense-mediated mRNA decay and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening. (less)
Pathogenic (Mar 30, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Not provided Affected status: yes Allele origin: germline	AiLife Diagnostics, AiLife Diagnostics Accession: SCV002502680.1 First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022	Publications: PubMed (25) PubMed: 2236053‚ 29261177‚ 9630075‚ 31036917‚ 30602999‚ 31589614‚ 18456578‚ 25333069‚ 7545856‚ 31980526‚ 22975760‚ 23951356‚ 19885835‚ 10639207‚ 22658665‚ 32281737‚ 32429104‚ 30487145‚ 23974870‚ 21520337‚ 25087612‚ 29298718‚ 23378603‚ 9806422‚ 25525159 Number of individuals with the variant: 1 Secondary finding: no
Pathogenic (May 12, 2021)	criteria provided, single submitter (Sema4 Curation Guidelines) Method: curation	Hereditary pancreatitis Affected status: unknown Allele origin: germline	Sema4, Sema4 Accession: SCV002529720.1 First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 Comment: The CFTR c.3846G>A (p.W1282X) variant has been reported as a common pathogenic variant in individuals with cystic fibrosis in the CFTR2 databases and in the … (more) The CFTR c.3846G>A (p.W1282X) variant has been reported as a common pathogenic variant in individuals with cystic fibrosis in the CFTR2 databases and in the literature(PMID: 32429104); This variant creates a premature stop codon at residue 1282 of the CFTR protein. At this location, this is predicted to cause nonsense-mediated decay and result in an absent protein (loss of function). Loss of function variants in CFTR are known to be pathogenic (PMID: 1695717). This variant was observed in 100/10360 chromosomes of the Ashkenazi Jewish subpopulation in the large and broad cohorts of the Genome Aggregation Database (http://gnomad.broadinstitute.org, PMID: 32461654) and has been reported in ClinVar (Variation ID 7129). Based on the current evidence available, this variant is interpreted as pathogenic. (less)	Publications: PubMed (2) PubMed: 32429104‚ 1695717
Pathogenic (Nov 05, 2018)	criteria provided, single submitter (Mendelics Assertion Criteria 2017) Method: clinical testing	Cystic fibrosis Affected status: yes Allele origin: unknown	Mendelics Accession: SCV000886191.2 First in ClinVar: Oct 10, 2018 Last updated: Dec 11, 2022
Pathogenic (Mar 30, 2021)	criteria provided, single submitter (Quest Diagnostics criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV000888091.4 First in ClinVar: Mar 13, 2019 Last updated: Jan 06, 2024	Publications: PubMed (33) PubMed: 10639207‚ 18456578‚ 19885835‚ 21520337‚ 2210768‚ 1721624‚ 1370365‚ 15371902‚ 11280952‚ 2236053‚ 22658665‚ 22975760‚ 23378603‚ 23974870‚ 25087612‚ 25333069‚ 25525159‚ 30487145‚ 30602999‚ 31036917‚ 31589614‚ 31980526‚ 32281737‚ 32429104‚ 7545856‚ 9630075‚ 9806422‚ 23951356‚ 21416780‚ 18639722‚ 29298718‚ 29261177‚ 27895116 Comment: The CFTR c.3846G>A (p.Trp1282, or W1282X) variant causes the premature termination of CFTR protein synthesis. In the published literature, this variant is associated with severe … (more) The CFTR c.3846G>A (p.Trp1282, or W1282X) variant causes the premature termination of CFTR protein synthesis. In the published literature, this variant is associated with severe pancreatic insufficient CF, classic CF, and is the most prevalent CF pathogenic variant in the Ashkenazi Jewish population (PMIDs: 29298718 (2018), 23951356 (2013), 21416780 2010), 1370365 (1992)). The frequency of this variant in the general population, 0.0097 (100/10360 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is consistent with pathogenicity. Based on the available information, this variant is classified as pathogenic. (less)
Pathogenic (Dec 08, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Revvity Omics, Revvity Accession: SCV002019239.3 First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024
Pathogenic (Jan 30, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Cystic fibrosis Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000075007.12 First in ClinVar: Jul 03, 2013 Last updated: Feb 20, 2024	Publications: PubMed (7) PubMed: 28492532‚ 1695717‚ 7691345‚ 9725922‚ 2475911‚ 15371902‚ 23974870 Comment: This sequence change creates a premature translational stop signal (p.Trp1282) in the CFTR gene. It is expected to result in an absent or disrupted protein … (more) This sequence change creates a premature translational stop signal (p.Trp1282) 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 present in population databases (rs77010898, gnomAD 0.9%). This premature translational stop signal has been observed in individual(s) with cystic fibrosis (CF). It is included in the American College of Medical Genetics (ACMG) panel of CF variants. It is one of the most common causes of cystic fibrosis. (PMID: 2475911, 15371902, 23974870). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It is commonly reported in individuals of Ashkenazi Jewish ancestry (PMID: 2475911, 15371902, 23974870). This variant is also known as W1282X. ClinVar contains an entry for this variant (Variation ID: 7129). For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Mar 15, 2023)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV000603029.4 First in ClinVar: Sep 30, 2017 Last updated: Feb 20, 2024	Comment: The CFTR c.3846G>A; p.Trp1282Ter variant (rs77010898) is reported in numerous individuals with cystic fibrosis and commonly associated with pancreatic insufficiency (see CFTR database, Kerem 1990, … (more) The CFTR c.3846G>A; p.Trp1282Ter variant (rs77010898) is reported in numerous individuals with cystic fibrosis and commonly associated with pancreatic insufficiency (see CFTR database, Kerem 1990, Shoshani 1992). This variant is also reported in ClinVar (Variation ID: 7129). It is observed in the general population with an overall allele frequency of 0.04% (121/282282 alleles) in the Genome Aggregation Database. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: CFTR2 database: https://cftr2.org/ Kerem BS et al. Identification of mutations in regions corresponding to the two putative nucleotide (ATP)-binding folds of the cystic fibrosis gene. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8447-51. PMID: 2236053. Shoshani T et al. Association of a nonsense mutation (W1282X), the most common mutation in the Ashkenazi Jewish cystic fibrosis patients in Israel, with presentation of severe disease. Am J Hum Genet. 1992 Jan;50(1):222-8. PMID: 1370365. (less)
Pathogenic (Mar 03, 2022)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Cystic fibrosis Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV002625848.2 First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024	Comment: The p.W1282* pathogenic mutation (also known as c.3846G>A), located in coding exon 23 of the CFTR gene, results from a G to A substitution at … (more) The p.W1282* pathogenic mutation (also known as c.3846G>A), located in coding exon 23 of the CFTR gene, results from a G to A substitution at nucleotide position 3846. This changes the amino acid from a tryptophan to a stop codon within coding exon 23. This alteration was originally reported in two individuals with cystic fibrosis, one with p.F508del as the second mutation and the other with an unknown second mutation (Vidaud M et al. Hum Genet. 1990;85(4):446-449). This alteration is also associated with pancreatic insufficiency, elevated sweat chloride levels, and higher rate of Pseudomonas infection (Sosnay PR et al. Nat Genet. 2013;45(10):1160-1167). Of note, this alteration is also known as 3978G>A in published literature. 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)
Pathogenic (Oct 31, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hereditary pancreatitis Bronchiectasis with or without elevated sweat chloride 1 Cystic fibrosis Congenital bilateral aplasia of vas deferens from CFTR mutation Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV000893748.1 First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019	Publications: PubMed (1) PubMed: 25741868 pmc: 4544753 pmc: 4544753 DOI: 10.1038/gim.2015.30 DOI: 10.1038/gim.2015.30
Pathogenic (Jul 12, 2018)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000329252.6 First in ClinVar: Dec 06, 2016 Last updated: Apr 17, 2019	Comment: The W1282X pathogenic variant in the CFTR gene is one of the most common variants associated with classic cystic fibrosis, including pancreatic insufficiency, when found … (more) The W1282X pathogenic variant in the CFTR gene is one of the most common variants associated with classic cystic fibrosis, including pancreatic insufficiency, when found in a homozygous state or when compound heterozygous with another CFTR pathogenic variant (Moskowitz et al., 2008; Kerem et al., 1990). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. W1282X was not observed at any significant frequency in approximately 6500 individuals of European and African American ancestry by the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The pathogenic variant was not present in the homozygous state within this population. We interpret W1282X as a pathogenic variant. (less)
Pathogenic (Sep 18, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 09 May 2019) Method: clinical testing	CFTR-Related Disorders Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000915208.1 First in ClinVar: May 27, 2019 Last updated: May 27, 2019	Publications: PubMed (3) PubMed: 1370365‚ 2210768‚ 8825494 Comment: The CFTR c.3846G>A (p.Trp1282Ter) variant is a stop-gained variant that is predicted to result in a premature termination of the protein. The variant was first … (more) The CFTR c.3846G>A (p.Trp1282Ter) variant is a stop-gained variant that is predicted to result in a premature termination of the protein. The variant was first reported by Vidaud et al. (1990) in one patient with cystic fibrosis who was a compound heterozygote for the p.Trp1282Ter variant and the common pathogenic p.Phe508del variant. Shoshani et al. (1992) later reported the p.Trp1282Ter variant on 63 chromosomes from 119 Israeli cystic fibrosis patients from 97 families, establishing the p.Trp1282Ter variant as the most common cystic fibrosis variant in the Ashkenazi Jewish population in Israel. Zielenski et al. (1995) published data from the Cystic Fibrosis Genetic Analysis Consortium showing that the p.Trp1282Ter variant appears in 535 of 43,849 CF chromosomes, with an overall frequency of 1.2%, and is the fifth most common disease-causing mutation in cystic fibrosis. ACMG guidelines published in 2004 recommend the p.Trp1282Ter variant be included in standard cystic fibrosis carrier screening. The variant is reported at a frequency of 0.00897 in the Ashkenazi Jewish population of the Genome Aggregation Database. Based on the collective evidence, the p.Trp1282Ter variant is classified as pathogenic for CFTR-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
Pathogenic (Jul 29, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Cystic fibrosis Affected status: unknown Allele origin: germline	Genome Diagnostics Laboratory, The Hospital for Sick Children Accession: SCV002507326.1 First in ClinVar: May 16, 2022 Last updated: May 16, 2022
Pathogenic (Mar 02, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Cystic fibrosis Affected status: yes Allele origin: inherited	Institute of Human Genetics, University of Leipzig Medical Center Accession: SCV003921079.1 First in ClinVar: May 06, 2023 Last updated: May 06, 2023	Comment: Criteria applied: PVS1, PS3, PM3_VSTR, PM2_SUP
Pathogenic (Mar 29, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Not provided Affected status: unknown Allele origin: germline	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV001713437.3 First in ClinVar: Jun 15, 2021 Last updated: Jun 09, 2024	Other databases https://cftr2.org/mutation/scien… https://cftr2.org/mutation/scientific/W1282X/ Number of individuals with the variant: 7
Pathogenic (Feb 09, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Cystic fibrosis Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV005049866.1 First in ClinVar: Jun 09, 2024 Last updated: Jun 09, 2024
Pathogenic (Feb 01, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: curation	Cystic fibrosis Affected status: no Allele origin: germline	Laboratory of Medical Genetics, National & Kapodistrian University of Athens Accession: SCV005052063.1 First in ClinVar: Jun 17, 2024 Last updated: Jun 17, 2024
Pathogenic (Mar 29, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Bronchiectasis with or without elevated sweat chloride 1 Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV004213268.2 First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024
Pathogenic (Oct 01, 2023)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV004160969.10 First in ClinVar: Nov 20, 2023 Last updated: Oct 20, 2024	Comment: CFTR: PVS1, PS4 Number of individuals with the variant: 1
Pathogenic (Jan 30, 2003)	no assertion criteria provided Method: literature only	CYSTIC FIBROSIS Affected status: not provided Allele origin: germline	OMIM Accession: SCV000027750.4 First in ClinVar: Apr 04, 2013 Last updated: Oct 06, 2019	Publications: PubMed (4) PubMed: 2210768‚ 1370365‚ 7520798‚ 12503104 Hamosh, A. Personal Communication. (more...) Hamosh, A. Personal Communication. 2018. Baltimore, Md. Comment on evidence: In a French patient with cystic fibrosis (CF; 219700), Vidaud et al. (1990) identified the substitution of tryptophan-1282 by a termination codon in the CFTR … (more) In a French patient with cystic fibrosis (CF; 219700), Vidaud et al. (1990) identified the substitution of tryptophan-1282 by a termination codon in the CFTR gene. The other chromosome carried the delta-F508 mutation (602421.0001). In another French patient with cystic fibrosis, Vidaud et al. (1990) found precisely the same mutation on one chromosome but the mutation on the other chromosome was unknown. A G-to-A substitution at nucleotide 3978 was responsible for the trp1282-to-ter change. Hamosh et al. (1991) cited evidence that the W1282X mutation, located in exon 20, is the most common CF mutation in the Ashkenazi Jewish population where it is present on 50% of CF chromosomes. In Israel, Shoshani et al. (1992) found the W1282X mutation in 63 chromosomes from 97 CF families. Sixteen patients homozygous for the W1282X mutation and 22 patients heterozygous for the delta-F508 and W1282X mutations had similarly severe disease, reflected by pancreatic insufficiency, high incidence of meconium ileus (37% and 27%, respectively), early age at diagnosis, poor nutritional status, and variable pulmonary function. Again, the W1282X mutation was the most common form in Ashkenazi Jewish patients in Israel. In the Jewish Ashkenazi patient population, 60% of the CF chromosomes carry the W1282X nonsense mutation. Patients homozygous for this mutation have severe disease with variable pulmonary complications. Studies by Shoshani et al. (1994) demonstrated that CFTR mRNA levels in patients homozygous for the W1282X mutation are not significantly decreased by the mutation. In patients heterozygous for the mutation, the relative levels of mRNA with the W1282X allele and either the delta-F508 or the normal allele were similar in each patient. These results indicated that the severe clinical phenotype of patients carrying the W1282X mutation is not due to a severe deficiency of mRNA. The severity, progression, and variability of the pulmonary disease appear to be affected by other, as yet unknown factors. Kulczycki et al. (2003) described their oldest patient with cystic fibrosis, a 71-year-old white male who had been diagnosed at the age of 27 years because of recurrent nasal polyposis, elevated sweat sodium and chloride, and a history of CF in his sister. Urologic examination demonstrated congenital bilateral absence of the vas deferens (277180). At the age of 60 years, genetic testing indicated compound heterozygosity for a severe W1282X mutation and a mild ala445-to-glu (602421.0130) mutation in the CFTR gene. (In the article by Kulczycki et al. (2003), the W1282X mutation was erroneously cited as H1282X.) (less)
Pathogenic (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001742913.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021
Pathogenic (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	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: SCV001957724.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021
Pathogenic (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001971640.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021
Pathogenic (Jul 29, 2019)	no assertion criteria provided Method: clinical testing	CFTR-related disorders Affected status: unknown Allele origin: germline	Genome Diagnostics Laboratory, The Hospital for Sick Children Accession: SCV002507410.1 First in ClinVar: May 16, 2022 Last updated: May 16, 2022
Pathogenic (-)	no assertion criteria provided Method: research	Cystic fibrosis Affected status: yes Allele origin: unknown	Genomics And Bioinformatics Analysis Resource, Columbia University Accession: SCV004024140.1 First in ClinVar: Aug 13, 2023 Last updated: Aug 13, 2023 Comment: Compound Heterozygous
Pathogenic (Jul 03, 2024)	no assertion criteria provided Method: clinical testing	CFTR-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV005355762.1 First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024	Comment: The CFTR c.3846G>A variant is predicted to result in premature protein termination (p.Trp1282). This variant has been reported to be causative for cystic fibrosis in … (more) The CFTR c.3846G>A variant is predicted to result in premature protein termination (p.Trp1282). This variant has been reported to be causative for cystic fibrosis in several individuals (see for example, Grody et al. 2001. PubMed ID: 11280952; Sosnay et al. 2013. PubMed ID: 23974870). This variant is reported in 0.97% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. Nonsense variants in CFTR are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
not provided (-)	no classification provided Method: phenotyping only	Cystic fibrosis Affected status: unknown Allele origin: unknown	GenomeConnect, ClinGen Accession: SCV001338859.1 First in ClinVar: Jun 22, 2020 Last updated: Jun 22, 2020	Comment: Variant interpretted as Pathogenic and reported on 11-16-2013 by Lab or GTR ID 320494. GenomeConnect assertions are reported exactly as they appear on the patient-provided … (more) Variant interpretted as Pathogenic and reported on 11-16-2013 by Lab or GTR ID 320494. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. (less) Clinical Features: Ptosis (present) , Hyperacusis (present) , Vertigo (present) , Abnormality of coordination (present) , Hypertonia (present) , Generalized hypotonia (present) , Movement disorder (present) , … (more) Ptosis (present) , Hyperacusis (present) , Vertigo (present) , Abnormality of coordination (present) , Hypertonia (present) , Generalized hypotonia (present) , Movement disorder (present) , Anxiety (present) , Hypohidrosis (present) , Joint hypermobility (present) , Abnormality of the curvature of the vertebral column (present) , Abnormality of muscle physiology (present) , Abnormality of the musculature of the limbs (present) , Abnormality of the musculature (present) , Abnormality of the somatic nervous system (present) , Abnormality of the cardiovascular system (present) , Hypercholesterolemia (present) , Asthma (present) , Abnormality of the diaphragm (present) , Abnormality of esophagus morphology (present) , Abnormality of the stomach (present) , Abnormality of the liver (present) , Gastrointestinal dysmotility (present) , Abnormality of the intestine (present) , Abnormality of the female genitalia (present) , Abnormality of reproductive system physiology (present) , Bruising susceptibility (present) , Epistaxis (present) (less) Indication for testing: Carrier Screening Age: 20-29 years Sex: female Testing laboratory: Counsyl Date variant was reported to submitter: 2013-11-16 Testing laboratory interpretation: Pathogenic
not provided (-)	no classification provided Method: literature only	Cystic fibrosis Affected status: unknown Allele origin: unknown	GeneReviews Accession: SCV001622793.2 First in ClinVar: May 23, 2021 Last updated: Oct 01, 2022	Publications: PubMed (2) PubMed: 20301428‚ 15371902 BookShelf: NBK1250 BookShelf: NBK1250
not provided (-)	no classification provided Method: phenotyping only	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. Affected status: unknown Allele origin: unknown	GenomeConnect - Invitae Patient Insights Network Accession: SCV001749739.2 First in ClinVar: Jul 18, 2021 Last updated: Jun 17, 2024	Comment: Variant interpreted as Pathogenic and reported on 03-06-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report … (more) Variant interpreted as Pathogenic and reported on 03-06-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. (less) Clinical Features: Hyperthyroidism (present) , Abnormality of the bladder (present) , Abnormal delivery (present) Indication for testing: Family Testing Age: 70-79 years Sex: female Testing laboratory: Invitae Date variant was reported to submitter: 2020-03-06 Testing laboratory interpretation: Pathogenic
click to load more click to collapse

Comment:

The Trp1282X variant in CFTR has been identified in numerous patients with cystic fibrosis (Viduad 1990, Kerem 1990, Hamosh 1991, Shoshani 1992). This variant is present on the American Board of Medical Genetics CFTR mutation panel (http://www.acmg.net/Pages/ACMG_Activities/stds-2002/cf.htm). This nonsense variant leads to a premature termination codon at position 1282, which is predicted to lead to a truncated or absent protein. In summary, this variant meets our criteria for pathogenicity.

Comment:

Variant summary: The CFTR c.3846G>A (p.Trp1282X) variant results in a premature termination codon, predicted to cause a truncated or absent CFTR protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant was found in 46/120654 control chromosomes at a frequency of 0.0003813, which does not exceed the estimated maximal expected allele frequency of a pathogenic CFTR variant (0.0129603). The variant is a common disease variant reported in numerous affected individuals in the literature. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic, including CFTR2. Taken together, this variant is classified as pathogenic.

Comment:

NM_000492.3(CFTR):c.3846G>A(W1282) is classified as pathogenic in the context of cystic fibrosis and is associated with the classic form of disease. Sources cited for classification include the following: PMID: 23974870. Classification of NM_000492.3(CFTR):c.3846G>A(W1282) is based on the following criteria: The variant causes a premature termination codon that is expected to be targeted by nonsense-mediated mRNA decay and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening.

Comment:

The CFTR c.3846G>A (p.Trp1282*, or W1282X) variant causes the premature termination of CFTR protein synthesis. In the published literature, this variant is associated with severe pancreatic insufficient CF, classic CF, and is the most prevalent CF pathogenic variant in the Ashkenazi Jewish population (PMIDs: 29298718 (2018), 23951356 (2013), 21416780 2010), 1370365 (1992)). The frequency of this variant in the general population, 0.0097 (100/10360 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is consistent with pathogenicity. Based on the available information, this variant is classified as pathogenic.

Comment:

This sequence change creates a premature translational stop signal (p.Trp1282*) 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 present in population databases (rs77010898, gnomAD 0.9%). This premature translational stop signal has been observed in individual(s) with cystic fibrosis (CF). It is included in the American College of Medical Genetics (ACMG) panel of CF variants. It is one of the most common causes of cystic fibrosis. (PMID: 2475911, 15371902, 23974870). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It is commonly reported in individuals of Ashkenazi Jewish ancestry (PMID: 2475911, 15371902, 23974870). This variant is also known as W1282X. ClinVar contains an entry for this variant (Variation ID: 7129). For these reasons, this variant has been classified as Pathogenic.

Comment:

The CFTR c.3846G>A; p.Trp1282Ter variant (rs77010898) is reported in numerous individuals with cystic fibrosis and commonly associated with pancreatic insufficiency (see CFTR database, Kerem 1990, Shoshani 1992). This variant is also reported in ClinVar (Variation ID: 7129). It is observed in the general population with an overall allele frequency of 0.04% (121/282282 alleles) in the Genome Aggregation Database. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: CFTR2 database: https://cftr2.org/ Kerem BS et al. Identification of mutations in regions corresponding to the two putative nucleotide (ATP)-binding folds of the cystic fibrosis gene. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8447-51. PMID: 2236053. Shoshani T et al. Association of a nonsense mutation (W1282X), the most common mutation in the Ashkenazi Jewish cystic fibrosis patients in Israel, with presentation of severe disease. Am J Hum Genet. 1992 Jan;50(1):222-8. PMID: 1370365.

Comment:

The p.W1282* pathogenic mutation (also known as c.3846G>A), located in coding exon 23 of the CFTR gene, results from a G to A substitution at nucleotide position 3846. This changes the amino acid from a tryptophan to a stop codon within coding exon 23. This alteration was originally reported in two individuals with cystic fibrosis, one with p.F508del as the second mutation and the other with an unknown second mutation (Vidaud M et al. Hum Genet. 1990;85(4):446-449). This alteration is also associated with pancreatic insufficiency, elevated sweat chloride levels, and higher rate of Pseudomonas infection (Sosnay PR et al. Nat Genet. 2013;45(10):1160-1167). Of note, this alteration is also known as 3978G>A in published literature. 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.

Comment:

The W1282X pathogenic variant in the CFTR gene is one of the most common variants associated with classic cystic fibrosis, including pancreatic insufficiency, when found in a homozygous state or when compound heterozygous with another CFTR pathogenic variant (Moskowitz et al., 2008; Kerem et al., 1990). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. W1282X was not observed at any significant frequency in approximately 6500 individuals of European and African American ancestry by the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The pathogenic variant was not present in the homozygous state within this population. We interpret W1282X as a pathogenic variant.

Comment:

The CFTR c.3846G>A (p.Trp1282Ter) variant is a stop-gained variant that is predicted to result in a premature termination of the protein. The variant was first reported by Vidaud et al. (1990) in one patient with cystic fibrosis who was a compound heterozygote for the p.Trp1282Ter variant and the common pathogenic p.Phe508del variant. Shoshani et al. (1992) later reported the p.Trp1282Ter variant on 63 chromosomes from 119 Israeli cystic fibrosis patients from 97 families, establishing the p.Trp1282Ter variant as the most common cystic fibrosis variant in the Ashkenazi Jewish population in Israel. Zielenski et al. (1995) published data from the Cystic Fibrosis Genetic Analysis Consortium showing that the p.Trp1282Ter variant appears in 535 of 43,849 CF chromosomes, with an overall frequency of 1.2%, and is the fifth most common disease-causing mutation in cystic fibrosis. ACMG guidelines published in 2004 recommend the p.Trp1282Ter variant be included in standard cystic fibrosis carrier screening. The variant is reported at a frequency of 0.00897 in the Ashkenazi Jewish population of the Genome Aggregation Database. Based on the collective evidence, the p.Trp1282Ter variant is classified as pathogenic for CFTR-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

Comment:

The CFTR c.3846G>A variant is predicted to result in premature protein termination (p.Trp1282*). This variant has been reported to be causative for cystic fibrosis in several individuals (see for example, Grody et al. 2001. PubMed ID: 11280952; Sosnay et al. 2013. PubMed ID: 23974870). This variant is reported in 0.97% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. Nonsense variants in CFTR are expected to be pathogenic. This variant is interpreted as pathogenic.

Comment:

Variant interpretted as Pathogenic and reported on 11-16-2013 by Lab or GTR ID 320494. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

Comment:

Variant interpreted as Pathogenic and reported on 03-06-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Analysis of CFTR Mutation Spectrum in Ethnic Russian Cystic Fibrosis Patients.	Petrova NV	Genes	2020	PMID: 32429104
Ataluren/ivacaftor combination therapy: Two N-of-1 trials in cystic fibrosis patients with nonsense mutations.	Peabody Lever JE	Pediatric pulmonology	2020	PMID: 32281737
Precision medicine integrating whole-genome sequencing, comprehensive metabolomics, and advanced imaging.	Hou YC	Proceedings of the National Academy of Sciences of the United States of America	2020	PMID: 31980526
Optimizing clinical exome design and parallel gene-testing for recessive genetic conditions in preconception carrier screening: Translational research genomic data from 14,125 exomes.	Capalbo A	PLoS genetics	2019	PMID: 31589614
Sequencing as a first-line methodology for cystic fibrosis carrier screening.	Beauchamp KA	Genetics in medicine : official journal of the American College of Medical Genetics	2019	PMID: 31036917
Cystic fibrosis in Tunisian children: a review of 32 children.	Boussetta K	African health sciences	2018	PMID: 30602999
High-frequency actionable pathogenic exome variants in an average-risk cohort.	Rego S	Cold Spring Harbor molecular case studies	2018	PMID: 30487145
S737F is a new CFTR mutation typical of patients originally from the Tuscany region in Italy.	Terlizzi V	Italian journal of pediatrics	2018	PMID: 29298718
Reproductive genetic carrier screening for cystic fibrosis, fragile X syndrome, and spinal muscular atrophy in Australia: outcomes of 12,000 tests.	Archibald AD	Genetics in medicine : official journal of the American College of Medical Genetics	2018	PMID: 29261177
Correctors and Potentiators Rescue Function of the Truncated W1282X-Cystic Fibrosis Transmembrane Regulator (CFTR) Translation Product.	Haggie PM	The Journal of biological chemistry	2017	PMID: 27895116
Therapeutic benefit observed with the CFTR potentiator, ivacaftor, in a CF patient homozygous for the W1282X CFTR nonsense mutation.	Mutyam V	Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society	2017	PMID: 27707539
RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease.	Xiong HY	Science (New York, N.Y.)	2015	PMID: 25525159
Disease variants in genomes of 44 centenarians.	Freudenberg-Hua Y	Molecular genetics & genomic medicine	2014	PMID: 25333069
Pathogenic variants for Mendelian and complex traits in exomes of 6,517 European and African Americans: implications for the return of incidental results.	Tabor HK	American journal of human genetics	2014	PMID: 25087612
Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene.	Sosnay PR	Nature genetics	2013	PMID: 23974870
A conservative assessment of the major genetic causes of idiopathic chronic pancreatitis: data from a comprehensive analysis of PRSS1, SPINK1, CTRC and CFTR genes in 253 young French patients.	Masson E	PloS one	2013	PMID: 23951356
CFTR p.Arg117His associated with CBAVD and other CFTR-related disorders.	Thauvin-Robinet C	Journal of medical genetics	2013	PMID: 23378603
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
Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in pancreatitis.	Ooi CY	Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society	2012	PMID: 22658665
Common CFTR haplotypes and susceptibility to chronic pancreatitis and congenital bilateral absence of the vas deferens.	Steiner B	Human mutation	2011	PMID: 21520337
CFTR allelic heterogeneity in Mexican patients with cystic fibrosis: implications for molecular screening.	Chávez-Saldaña M	Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion	2010	PMID: 21416780
Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and risk for pancreatic adenocarcinoma.	McWilliams RR	Cancer	2010	PMID: 19885835
Guidelines for diagnosis of cystic fibrosis in newborns through older adults: Cystic Fibrosis Foundation consensus report.	Farrell PM	The Journal of pediatrics	2008	PMID: 18639722
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
Mutations in the cystic fibrosis transmembrane regulator gene and in vivo transepithelial potentials.	Wilschanski M	American journal of respiratory and critical care medicine	2006	PMID: 16840743
Genotype-phenotype correlation for pulmonary function in cystic fibrosis.	de Gracia J	Thorax	2005	PMID: 15994263
Cystic fibrosis population carrier screening: 2004 revision of American College of Medical Genetics mutation panel.	Watson MS	Genetics in medicine : official journal of the American College of Medical Genetics	2004	PMID: 15371902
Effect of genotype on phenotype and mortality in cystic fibrosis: a retrospective cohort study.	McKone EF	Lancet (London, England)	2003	PMID: 12767731
A clinical perspective of cystic fibrosis and new genetic findings: relationship of CFTR mutations to genotype-phenotype manifestations.	Kulczycki LL	American journal of medical genetics. Part A	2003	PMID: 12503104
Laboratory standards and guidelines for population-based cystic fibrosis carrier screening.	Grody WW	Genetics in medicine : official journal of the American College of Medical Genetics	2001	PMID: 11280952
Severe allergic bronchopulmonary aspergillosis in an infant with cystic fibrosis and her asthmatic father.	Mussaffi H	Pediatric pulmonology	2000	PMID: 10639207
The association of nonsense codons with exon skipping.	Valentine CR	Mutation research	1998	PMID: 9806422
Relation between mutations of the cystic fibrosis gene and idiopathic pancreatitis.	Cohn JA	The New England journal of medicine	1998	PMID: 9725922
Congenital bilateral absence of vas deferens with a new missense mutation (P499A) in the CFTR gene.	Arduino C	Clinical genetics	1998	PMID: 9630075
Cystic fibrosis: genotypic and phenotypic variations.	Zielenski J	Annual review of genetics	1995	PMID: 8825494
Molecular and clinical findings in Austrian cystic fibrosis patients with mutations in exon 11 of the CFTR gene.	Greil I	Wiener klinische Wochenschrift	1995	PMID: 7545856
Two novel mutations in the CFTR gene: W1089X in exon 17B and 4010delTATT in exon 21.	Shoshani T	Human molecular genetics	1994	PMID: 7520798
Molecular basis of defective anion transport in L cells expressing recombinant forms of CFTR.	Yang Y	Human molecular genetics	1993	PMID: 7691345
Association of a nonsense mutation (W1282X), the most common mutation in the Ashkenazi Jewish cystic fibrosis patients in Israel, with presentation of severe disease.	Shoshani T	American journal of human genetics	1992	PMID: 1370365
Severe deficiency of cystic fibrosis transmembrane conductance regulator messenger RNA carrying nonsense mutations R553X and W1316X in respiratory epithelial cells of patients with cystic fibrosis.	Hamosh A	The Journal of clinical investigation	1991	PMID: 1721624
Identification of mutations in regions corresponding to the two putative nucleotide (ATP)-binding folds of the cystic fibrosis gene.	Kerem BS	Proceedings of the National Academy of Sciences of the United States of America	1990	PMID: 2236053
Three point mutations in the CFTR gene in French cystic fibrosis patients: identification by denaturing gradient gel electrophoresis.	Vidaud M	Human genetics	1990	PMID: 2210768
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
Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA.	Riordan JR	Science (New York, N.Y.)	1989	PMID: 2475911
Hamosh, A. Personal Communication. 2018. Baltimore, Md.	-	-	-	-
http://www.cftr2.org/	-	-	-	-
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CFTR	-	-	-	-
https://cftr2.org	-	-	-	-
https://cftr2.org/mutation/scientific/W1282X/	-	-	-	-
click to load more click to collapse

Text-mined citations for rs77010898 ...

These 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 Nov 03, 2024

ClinVar Genomic variation as it relates to human health

NM_000492.4(CFTR):c.3846G>A (p.Trp1282Ter)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs77010898 ...