VCV000007136.146 - ClinVar

NM_000492.4(CFTR):c.3909C>G (p.Asn1303Lys)

Germline

Top reviewed classifications are shown here.

Submission summary:

42 submissions

39 submitters

7 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

Identifiers

NM_000492.4(CFTR):c.3909C>G (p.Asn1303Lys)

Variation ID: 7136 Accession: VCV000007136.146

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 7q31.2 7: 117652877 (GRCh38) [ NCBI UCSC ] 7: 117292931 (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	Mar 24, 2015	Oct 20, 2024	Mar 3, 2004

HGVS

Nucleotide	Protein	Molecular consequence
NM_000492.4:c.3909C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000483.3:p.Asn1303Lys	missense
NC_000007.14:g.117652877C>G
NC_000007.13:g.117292931C>G
NG_016465.4:g.192094C>G
LRG_663:g.192094C>G
LRG_663t1:c.3909C>G	LRG_663p1:p.Asn1303Lys
	P13569:p.Asn1303Lys

... more HGVS ... less HGVS

Protein change

N1303K

Other names

Canonical SPDI

NC_000007.14:117652876:C:G

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.

0.00020 (G)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD), exomes 0.00014

Exome Aggregation Consortium (ExAC) 0.00015

1000 Genomes Project 30x 0.00016

The Genome Aggregation Database (gnomAD) 0.00016

1000 Genomes Project 0.00020

Trans-Omics for Precision Medicine (TOPMed) 0.00020

Links

dbSNP: rs80034486 ClinGen: CA340641 Genetic Testing Registry (GTR): GTR000074114 Genetic Testing Registry (GTR): GTR000257096 Genetic Testing Registry (GTR): GTR000500233 Genetic Testing Registry (GTR): GTR000576392 UniProtKB: P13569#VAR_000267 OMIM: 602421.0032 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	3826	5201

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 (21)	practice guideline	Mar 3, 2004	RCV000007556.50
not provided	Pathogenic (14)	criteria provided, multiple submitters, no conflicts	Oct 26, 2023	RCV000224445.59
Congenital bilateral aplasia of vas deferens from CFTR mutation Cystic fibrosis	Pathogenic (1)	criteria provided, single submitter	-	RCV001004513.9
Spermatogenic failure, Y-linked, 2	Pathogenic (1)	criteria provided, single submitter	Jun 7, 2018	RCV002287325.8
CFTR-related disorder	Pathogenic (3)	no assertion criteria provided	Jun 21, 2024	RCV001831530.14
Hereditary pancreatitis	Pathogenic (1)	criteria provided, single submitter	May 25, 2021	RCV002255995.9
Bronchiectasis with or without elevated sweat chloride 1	Pathogenic (1)	criteria provided, single submitter	Mar 29, 2024	RCV003473015.2

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: SCV000071408.2 First in ClinVar: Jun 04, 2013 Last updated: Mar 24, 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: SCV000071513.4 First in ClinVar: Oct 18, 2013 Last updated: Dec 26, 2017	Other databases https://cftr2.org https://cftr2.org
Pathogenic (Aug 29, 2014)	criteria provided, single submitter (Courtagen Life Sciences Classifications) Method: clinical testing	Cystic fibrosis Affected status: unknown Allele origin: germline	Courtagen Diagnostics Laboratory, Courtagen Life Sciences Accession: SCV000236515.2 First in ClinVar: Jul 05, 2015 Last updated: Jul 05, 2015
Pathogenic (Feb 11, 2015)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: not provided Allele origin: germline	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics Accession: SCV000280980.1 First in ClinVar: Jun 08, 2016 Last updated: Jun 08, 2016
Pathogenic (May 15, 2018)	criteria provided, single submitter (EGL ClinVar v180209 classification definitions) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000700266.2 First in ClinVar: Dec 26, 2017 Last updated: Dec 15, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CFTR Number of individuals with the variant: 10 Sex: mixed
Pathogenic (Nov 21, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Cystic fibrosis Affected status: unknown Allele origin: unknown	Equipe Genetique des Anomalies du Developpement, Université de Bourgogne Accession: SCV000883112.1 First in ClinVar: Oct 10, 2018 Last updated: Oct 10, 2018
Pathogenic (Dec 31, 2018)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000322329.7 First in ClinVar: Oct 09, 2016 Last updated: Apr 17, 2019	Comment: The N1303K variant in the CFTR gene has been reported previously as a CF-causing variant in patients with abnormal sweat chloride levels, pancreatic insufficiency, and … (more) The N1303K variant in the CFTR gene has been reported previously as a CF-causing variant in patients with abnormal sweat chloride levels, pancreatic insufficiency, and mild to moderate lung disease (Sosnay et al., 2013; Osborne et al, 1991). The N1303K variant was not observed at any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The N1303K variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position within the ABC transporter 2 domain that is conserved across species. Cell lines expressing the N1303K CFTR variant show loss of baseline chloride transport compared to those expressing wild type protein (Van Goor et al., 2014). A missense variant at the same residue, N1303H, was reported in a patient with severe pulmonary disease and pancreatic insufficiency (Claustres et al., 1992). We interpret N1303K as a pathogenic variant. (less)
Pathogenic (Sep 05, 2017)	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: SCV000466525.3 First in ClinVar: Dec 06, 2016 Last updated: May 27, 2019	Publications: PubMed (4) PubMed: 21520337‚ 21679131‚ 20301428‚ 23751316 Comment: The CFTR c.3909C>G (p.Asn1303Lys) missense variant is a well-known, widely reported pathogenic variant that accounts for approximately 1.3% of disease alleles, and is often associated … (more) The CFTR c.3909C>G (p.Asn1303Lys) missense variant is a well-known, widely reported pathogenic variant that accounts for approximately 1.3% of disease alleles, and is often associated with a classic cystic fibrosis (CF) phenotype (Ong et al. 2001). The Cystic Fibrosis Mutation Database (http://www.genet.sickkids.on.ca/cftr/Home.html) indicates that the p.Asn1303Lys variant is the fourth most common CFTR variant worldwide, and the Clinical and Functional Translation of CFTR (CFTR2) database (http://cftr2.org) reports the p.Asn1303Lys variant in over 2100 patients, noting that it is a cystic fibrosis-causing variant. Across a selection of the available literature, the p.Asn1303Lys variant has also been reported in five patients with congenital bilateral absence of the vas deferens (CBAVD), including three compound heterozygotes and two heterozygotes in whom a second variant was not identified (Steiner et al. 2011; Tomaiuolo et al. 2011), and in four patients with chronic pancreatitis, including three compound heterozygotes and one heterozygote (Steiner et al. 2011; Hamoir et al. 2013). The p.Asn1303Lys variant is reported at a frequency of 0.00035 in the European American population of the Exome Sequencing Project. Based on the collective evidence, the p.Asn1303Lys 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 (-)	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: SCV001163558.1 First in ClinVar: Mar 01, 2020 Last updated: Mar 01, 2020
Pathogenic (Oct 10, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Cystic fibrosis (Autosomal recessive inheritance) Affected status: yes Allele origin: inherited	Undiagnosed Diseases Network, NIH Accession: SCV001245580.1 First in ClinVar: May 12, 2020 Last updated: May 12, 2020	Publications: PubMed (13) PubMed: 25741868‚ 1998343‚ 22020151‚ 20865572‚ 21228398‚ 18456578‚ 15614862‚ 24440181‚ 26075213‚ 23751316‚ 22975760‚ 25489051‚ 23951356 pmc: 4544753 pmc: 4544753 DOI: 10.1038/gim.2015.30 DOI: 10.1038/gim.2015.30 Number of individuals with the variant: 1 Clinical Features: Ventriculomegaly (present) , Spastic diplegia (present) , Skeletal myopathy (present) , Skeletal muscle atrophy (present) , Short stature (present) , Polyhydramnios (present) , Pes cavus … (more) Ventriculomegaly (present) , Spastic diplegia (present) , Skeletal myopathy (present) , Skeletal muscle atrophy (present) , Short stature (present) , Polyhydramnios (present) , Pes cavus (present) , Myopathic facies (present) , Myoclonus (present) , Motor axonal neuropathy (present) , Moderate global developmental delay (present) , Midface retrusion (present) , Mandibular prognathia (present) , Flexion contracture (present) , Failure to thrive (present) , EMG: myopathic abnormalities (present) , Distal muscle weakness (present) , Absence seizures (present) , Abnormal morphology of the hippocampus (present) (less) Age: 20-29 years Sex: male Ethnicity/Population group: Hispanic Tissue: blood Testing laboratory: Baylor Genetics Date variant was reported to submitter: 2018-10-10 Testing laboratory interpretation: Pathogenic
Pathogenic (May 25, 2021)	criteria provided, single submitter (Sema4 Curation Guidelines) Method: curation	Hereditary pancreatitis Affected status: unknown Allele origin: germline	Sema4, Sema4 Accession: SCV002529722.1 First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 Comment: The CFTR c.3909C>G (p.N1303K) 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.3909C>G (p.N1303K) variant has been reported as a common pathogenic variant in individuals with cystic fibrosis in the CFTR2 databases and in the literature (PMID:1380943). It has also been reported in individuals with pancreatic cancer or pancreatitis (PMID:19885835, 22020151, 22658665). Functional studies showed that It caused loss of baseline chloride transport (PMID:23891399). It was observed in 6/10308 chromosomes in the Ashkenazi Jewish population according to the Genome Aggregation Database (http://gnomad.broadinstitute.org, PMID: 32461654) and has been reported in ClinVar (Variation ID: 7136). Based on the current evidence available, this variant is interpreted as pathogenic. (less)	Publications: PubMed (5) PubMed: 1380943‚ 19885835‚ 22020151‚ 22658665‚ 23891399
Pathogenic (Apr 27, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Cystic fibrosis Affected status: yes Allele origin: germline	MGZ Medical Genetics Center Accession: SCV002580775.1 First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 Comment: ACMG criteria applied: PM3_VSTR, PS4, PS3_SUP, PM2_SUP, PP3	Number of individuals with the variant: 1 Sex: female
Pathogenic (Sep 23, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Cystic fibrosis Affected status: yes Allele origin: germline	Human Genetics Bochum, Ruhr University Bochum Accession: SCV002758574.1 First in ClinVar: Dec 11, 2022 Last updated: Dec 11, 2022	Comment: ACMG criteria used to clasify this variant: PS3, PS4, PP3, PP1
Pathogenic (Sep 01, 2017)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Cystic fibrosis (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Baylor Genetics Accession: SCV000807601.2 First in ClinVar: Dec 26, 2017 Last updated: Dec 11, 2022	Publications: PubMed (2) PubMed: 25326635‚ 1998343 Comment: This mutation has been previously reported as disease-causing and was found once in our laboratory in a homozygous state in a 13-year-old male with a … (more) This mutation has been previously reported as disease-causing and was found once in our laboratory in a homozygous state in a 13-year-old male with a clinical diagnosis of cystic fibrosis. Heterozygotes are expected to be asymptomatic carriers. (less)
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: SCV000886186.2 First in ClinVar: Oct 10, 2018 Last updated: Dec 11, 2022
Pathogenic (Nov 03, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: not provided Allele origin: germline	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden Accession: SCV004026196.1 First in ClinVar: Aug 19, 2023 Last updated: Aug 19, 2023
Pathogenic (Jul 26, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: curation	Cystic fibrosis Affected status: yes Allele origin: unknown	Institute of Human Genetics, University of Leipzig Medical Center Accession: SCV002573872.2 First in ClinVar: Sep 24, 2022 Last updated: Sep 20, 2023	Comment: This variant was classified based on the report of 1 patient with a clinically confirmed diagnosis of cystic fibrosis in the context of re-classifying variants … (more) This variant was classified based on the report of 1 patient with a clinically confirmed diagnosis of cystic fibrosis in the context of re-classifying variants in the German Cystic Fibrosis Registry (Muko e.V.). Patients have not been seen personally, but only reports were evaluated. Criteria applied: PS3, PM2_SUP, PM3_VSTR, PM5_STR, PP3, PP4 (less) Number of individuals with the variant: 1
Pathogenic (Feb 22, 2023)	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: SCV004221697.1 First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024	Publications: PubMed (45) PubMed: 23974870‚ 11280952‚ 26208274‚ 23751316‚ 21679131‚ 15994263‚ 1380943‚ 1998343‚ 1712898‚ 26075213‚ 23891399‚ 26823392‚ 25799511‚ 11186891‚ 11484207‚ 11924117‚ 15357568‚ 15614862‚ 17127107‚ 1723032‚ 17348320‚ 18456578‚ 19885835‚ 20865572‚ 21228398‚ 21520337‚ 22020151‚ 22658665‚ 22975760‚ 23951356‚ 24440181‚ 25087612‚ 25489051‚ 28655774‚ 29208182‚ 29261177‚ 30293248‚ 31019283‚ 31036917‚ 31523618‚ 31589614‚ 32220772‚ 32429104‚ 34190021‚ 34426522 Comment: The frequency of this variant in the general population, 0.00018 (23/128054 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the … (more) The frequency of this variant in the general population, 0.00018 (23/128054 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in the homozygous state and with other CF variants in trans to be particularly associated with a pancreatic insufficient phenotype, however, variable lung function phenotypes from unusually mild to severe have been observed (PMID: 1380943 (1992), 23974870 (2013), and 26208274 (2015)). Functional analysis has described this variant as Class II causing defective protein processing, protein degradation, insignificant levels of mature CFTR, and conductance (PMID: 1712898 (1991), 23891399 (2014), 25799511 (2015), 26823392 (2016)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, this variant is classified as pathogenic. (less)
Pathogenic (Aug 22, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Revvity Omics, Revvity Accession: SCV002019227.3 First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024
Pathogenic (Jan 29, 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: SCV000075041.11 First in ClinVar: Jul 03, 2013 Last updated: Feb 14, 2024	Publications: PubMed (10) PubMed: 28492532‚ 1380943‚ 12767731‚ 15371902‚ 21520337‚ 22658665‚ 23951356‚ 23974870‚ 23891399‚ 25799511 Comment: This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 1303 of the CFTR protein (p.Asn1303Lys). … (more) This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 1303 of the CFTR protein (p.Asn1303Lys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individuals with CFTR-related disorders, including cystic fibrosis, congenital bilateral absence of the vas deferens, and chronic pancreatitis (PMID: 1380943, 12767731, 15371902, 21520337, 22658665, 23951356, 23974870). ClinVar contains an entry for this variant (Variation ID: 7136). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CFTR protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects CFTR function (PMID: 23891399, 23974870, 25799511). For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Oct 26, 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: SCV000885186.6 First in ClinVar: Feb 17, 2019 Last updated: Feb 20, 2024	Comment: The CFTR c.3909C>G; p.Asn1303Lys variant (rs80034486), is reported in the literature in multiple individuals diagnosed with cystic fibrosis, often associated with pancreatic insufficiency (Osborne 1991, … (more) The CFTR c.3909C>G; p.Asn1303Lys variant (rs80034486), is reported in the literature in multiple individuals diagnosed with cystic fibrosis, often associated with pancreatic insufficiency (Osborne 1991, Osborne 1992, Ooi 2012, Sosnay 2013, CFTR2 database). This variant is reported in ClinVar (Variation ID: 7136), and is found in the general population with an overall allele frequency of 0.014% (34/244424 alleles) in the Genome Aggregation Database. The asparagine at codon 1303 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.83). Functional characterization of the variant protein indicates a defect in CFTR processing, resulting in a severe reduction in chloride transport activity (Sosnay 2013, Van Goor 2014). Based on available information, this variant is considered to be pathogenic. References: CFTR2 database: http://cftr2.org Ooi C. et al. Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in pancreatitis. J Cyst Fibros. 2012 11(5):355-62. PMID: 22658665 Osborne L et al. A mutation in the second nucleotide binding fold of the cystic fibrosis gene. Am J Hum Genet. 1991 48(3):608-12. PMID: 1998343 Osborne L et al. Incidence and expression of the N1303K mutation of the cystic fibrosis (CFTR) gene. Hum Genet. 1992 89(6):653-8. PMID: 1380943 Sosnay PR et al. Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. Nat Genet. 2013 45(10):1160-7. PMID: 23974870 Van Goor F et al. Effect of ivacaftor on CFTR forms with missense mutations associated with defects in protein processing or function. J Cyst Fibros. 2014 13(1):29-36. PMID: 23891399 (less)
Uncertain significance (Apr 04, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Cystic fibrosis Affected status: unknown Allele origin: germline	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center Accession: SCV004810237.1 First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024
Pathogenic (Jan 31, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Not provided Affected status: unknown Allele origin: germline	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV001713441.2 First in ClinVar: Jun 15, 2021 Last updated: Jun 09, 2024	Other databases https://cftr2.org/ https://cftr2.org/ Number of individuals with the variant: 7
Pathogenic (Oct 01, 2019)	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: SCV001246824.26 First in ClinVar: May 12, 2020 Last updated: Oct 20, 2024	Number of individuals with the variant: 1
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: SCV001169352.1 First in ClinVar: Mar 16, 2020 Last updated: Mar 16, 2020	Publications: PubMed (1) PubMed: 28603918
Pathogenic (May 10, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: yes Allele origin: germline	Clinical Genetics and Genomics, Karolinska University Hospital Accession: SCV001450061.1 First in ClinVar: Dec 12, 2020 Last updated: Dec 12, 2020	Number of individuals with the variant: 1
Pathogenic (Sep 25, 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: SCV002507341.1 First in ClinVar: May 16, 2022 Last updated: May 16, 2022
Pathogenic (Jun 07, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Spermatogenic failure, Y-linked, 2 Affected status: yes Allele origin: unknown	Institute of Human Genetics, University Hospital Muenster Accession: SCV002577968.1 First in ClinVar: Oct 08, 2022 Last updated: Oct 08, 2022	Comment: ACMG categories: PS3,PS4,PP3,PP5 Number of individuals with the variant: 1 Age: 30-39 years Sex: male Tissue: blood
Pathogenic (Feb 03, 2016)	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015)) Method: clinical testing	Cystic fibrosis Affected status: unknown Allele origin: unknown	Counsyl Accession: SCV000485189.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 24, 2022
Pathogenic (Feb 18, 2022)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Cystic fibrosis Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV001183025.4 First in ClinVar: Mar 16, 2020 Last updated: May 01, 2024	Publications: PubMed (2) PubMed: 1380943‚ 1712898 Comment: The p.N1303K pathogenic mutation (also known as c.3909C>G), located in coding exon 24 of the CFTR gene, results from a C to G substitution at … (more) The p.N1303K pathogenic mutation (also known as c.3909C>G), located in coding exon 24 of the CFTR gene, results from a C to G substitution at nucleotide position 3909. The asparagine at codon 1303 is replaced by lysine, an amino acid with similar properties. In one study, this mutation was identified in 216 cystic fibrosis alleles, including 10 homozygous individuals with elevated sweat chloride levels and decreased lung function. Of the 6 homozygous individuals with reported pancreatic status, all were pancreatic insufficient (Osborne L et al. Hum. Genet., 1992 Aug;89:653-8). In vitro functional studies determined that this mutation prevents the maturation, trafficking, and subsequent activity of the CFTR protein (Gregory RJ et al. Mol. Cell. Biol., 1991 Aug;11:3886-93). This pathogenic mutation is associated with elevated sweat chloride levels, decreased lung function, and pancreatic insufficiency; in vitro functional studies showed this mutation results in significantly reduced chloride conductance (Sosnay PR et al. Nat. Genet., 2013 Oct;45:1160-7). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
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: SCV004213314.2 First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024
Pathogenic (May 27, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: yes Allele origin: germline	Clinical Genetics Laboratory, Skane University Hospital Lund Accession: SCV005197472.1 First in ClinVar: Aug 25, 2024 Last updated: Aug 25, 2024
Pathogenic (Aug 01, 1992)	no assertion criteria provided Method: literature only	CYSTIC FIBROSIS Affected status: not provided Allele origin: germline	OMIM Accession: SCV000027757.2 First in ClinVar: Apr 04, 2013 Last updated: Dec 26, 2017	Publications: PubMed (2) PubMed: 1998343‚ 1380943 Comment on evidence: On 4 of 52 chromosomes from patients with cystic fibrosis (CF; 219700), including 2 sibs, Osborne et al. (1991) identified a C-to-G change at nucleotide … (more) On 4 of 52 chromosomes from patients with cystic fibrosis (CF; 219700), including 2 sibs, Osborne et al. (1991) identified a C-to-G change at nucleotide 4041 of the CFTR gene resulting in a change from asparagine to lysine at amino acid position 1303 (N1303K). This mutation was found exclusively in heterozygous state and no correlation could be made between clinical phenotype and the presence of the gene. Pooling laboratories throughout Europe and the United States, Osborne et al. (1992) identified 216 examples of N1303K among nearly 15,000 CF chromosomes tested, a frequency of 1.5%. The frequency was greater in southern than in northern Europe; it was not found in U.K. Asians, American blacks, or Australians. Ten patients were homozygous, whereas 106 of the remainder carried 1 of 12 known CF mutations in the other allele. Osborne et al. (1992) concluded that N1303K is a 'severe' mutation with respect to the pancreas, but could find no correlation between this mutation in either the homozygous or heterozygous state and the severity of lung disease. (less)
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: SCV001975183.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021
Pathogenic (Mar 17, 2017)	no assertion criteria provided Method: clinical testing	CFTR-related disorders Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV002075912.1 First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022
Pathogenic (Jun 21, 2024)	no assertion criteria provided Method: clinical testing	CFTR-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004734204.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: The CFTR c.3909C>G variant is predicted to result in the amino acid substitution p.Asn1303Lys. This variant has been reported to be causative for cystic fibrosis … (more) The CFTR c.3909C>G variant is predicted to result in the amino acid substitution p.Asn1303Lys. This variant has been reported to be causative for cystic fibrosis (Sosnay et al. 2013. PubMed ID: 23974870; Masson et al. 2013. PubMed ID: 23951356; Osborne et al. 1991. PubMed ID: 1998343; Watson et al. 2004. PubMed ID: 15371902). This variant is reported in 0.058% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. This variant is interpreted as pathogenic. (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: SCV001740653.3 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: SCV001959836.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021
Pathogenic (Sep 25, 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: SCV002507425.1 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: SCV004024087.1 First in ClinVar: Aug 13, 2023 Last updated: Aug 13, 2023 Comment: Compound Heterozygous
not provided (-)	no classification provided Method: literature only	Cystic fibrosis Affected status: unknown Allele origin: unknown	GeneReviews Accession: SCV001622794.2 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 Affected status: unknown Allele origin: unknown	GenomeConnect, ClinGen Accession: SCV000986698.1 First in ClinVar: Sep 01, 2019 Last updated: Sep 01, 2019	Comment: Variant interpretted as pathogenic and reported on 03/20/2016 by GTR ID 500068. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from … (more) Variant interpretted as pathogenic and reported on 03/20/2016 by GTR ID 500068. 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: Abnormality of the ear (present) , Conductive hearing impairment (present) , Sensorineural hearing loss (present) , Mixed hearing impairment (present) , Hearing impairment (present) , … (more) Abnormality of the ear (present) , Conductive hearing impairment (present) , Sensorineural hearing loss (present) , Mixed hearing impairment (present) , Hearing impairment (present) , Tinnitus (present) , Hyperacusis (present) , Vertigo (present) , Bipolar affective disorder (present) , Anxiety (present) , Depressivity (present) , Short attention span (present) , Hypohidrosis (present) , Hyperhidrosis (present) , Abnormality of the pancreas (present) , Recurrent infections (present) (less) Age: 30-39 years Sex: female Testing laboratory: Mayo Clinic Laboratories,Mayo Clinic Date variant was reported to submitter: 2016-03-20 Testing laboratory interpretation: Pathogenic
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Comment:

The N1303K variant in the CFTR gene has been reported previously as a CF-causing variant in patients with abnormal sweat chloride levels, pancreatic insufficiency, and mild to moderate lung disease (Sosnay et al., 2013; Osborne et al, 1991). The N1303K variant was not observed at any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The N1303K variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position within the ABC transporter 2 domain that is conserved across species. Cell lines expressing the N1303K CFTR variant show loss of baseline chloride transport compared to those expressing wild type protein (Van Goor et al., 2014). A missense variant at the same residue, N1303H, was reported in a patient with severe pulmonary disease and pancreatic insufficiency (Claustres et al., 1992). We interpret N1303K as a pathogenic variant.

Comment:

The CFTR c.3909C>G (p.Asn1303Lys) missense variant is a well-known, widely reported pathogenic variant that accounts for approximately 1.3% of disease alleles, and is often associated with a classic cystic fibrosis (CF) phenotype (Ong et al. 2001). The Cystic Fibrosis Mutation Database (http://www.genet.sickkids.on.ca/cftr/Home.html) indicates that the p.Asn1303Lys variant is the fourth most common CFTR variant worldwide, and the Clinical and Functional Translation of CFTR (CFTR2) database (http://cftr2.org) reports the p.Asn1303Lys variant in over 2100 patients, noting that it is a cystic fibrosis-causing variant. Across a selection of the available literature, the p.Asn1303Lys variant has also been reported in five patients with congenital bilateral absence of the vas deferens (CBAVD), including three compound heterozygotes and two heterozygotes in whom a second variant was not identified (Steiner et al. 2011; Tomaiuolo et al. 2011), and in four patients with chronic pancreatitis, including three compound heterozygotes and one heterozygote (Steiner et al. 2011; Hamoir et al. 2013). The p.Asn1303Lys variant is reported at a frequency of 0.00035 in the European American population of the Exome Sequencing Project. Based on the collective evidence, the p.Asn1303Lys 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:

This mutation has been previously reported as disease-causing and was found once in our laboratory in a homozygous state in a 13-year-old male with a clinical diagnosis of cystic fibrosis. Heterozygotes are expected to be asymptomatic carriers.

Comment:

This variant was classified based on the report of 1 patient with a clinically confirmed diagnosis of cystic fibrosis in the context of re-classifying variants in the German Cystic Fibrosis Registry (Muko e.V.). Patients have not been seen personally, but only reports were evaluated. Criteria applied: PS3, PM2_SUP, PM3_VSTR, PM5_STR, PP3, PP4

Comment:

The frequency of this variant in the general population, 0.00018 (23/128054 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in the homozygous state and with other CF variants in trans to be particularly associated with a pancreatic insufficient phenotype, however, variable lung function phenotypes from unusually mild to severe have been observed (PMID: 1380943 (1992), 23974870 (2013), and 26208274 (2015)). Functional analysis has described this variant as Class II causing defective protein processing, protein degradation, insignificant levels of mature CFTR, and conductance (PMID: 1712898 (1991), 23891399 (2014), 25799511 (2015), 26823392 (2016)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, this variant is classified as pathogenic.

Comment:

This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 1303 of the CFTR protein (p.Asn1303Lys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individuals with CFTR-related disorders, including cystic fibrosis, congenital bilateral absence of the vas deferens, and chronic pancreatitis (PMID: 1380943, 12767731, 15371902, 21520337, 22658665, 23951356, 23974870). ClinVar contains an entry for this variant (Variation ID: 7136). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CFTR protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects CFTR function (PMID: 23891399, 23974870, 25799511). For these reasons, this variant has been classified as Pathogenic.

Comment:

The CFTR c.3909C>G; p.Asn1303Lys variant (rs80034486), is reported in the literature in multiple individuals diagnosed with cystic fibrosis, often associated with pancreatic insufficiency (Osborne 1991, Osborne 1992, Ooi 2012, Sosnay 2013, CFTR2 database). This variant is reported in ClinVar (Variation ID: 7136), and is found in the general population with an overall allele frequency of 0.014% (34/244424 alleles) in the Genome Aggregation Database. The asparagine at codon 1303 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.83). Functional characterization of the variant protein indicates a defect in CFTR processing, resulting in a severe reduction in chloride transport activity (Sosnay 2013, Van Goor 2014). Based on available information, this variant is considered to be pathogenic. References: CFTR2 database: http://cftr2.org Ooi C. et al. Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in pancreatitis. J Cyst Fibros. 2012 11(5):355-62. PMID: 22658665 Osborne L et al. A mutation in the second nucleotide binding fold of the cystic fibrosis gene. Am J Hum Genet. 1991 48(3):608-12. PMID: 1998343 Osborne L et al. Incidence and expression of the N1303K mutation of the cystic fibrosis (CFTR) gene. Hum Genet. 1992 89(6):653-8. PMID: 1380943 Sosnay PR et al. Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. Nat Genet. 2013 45(10):1160-7. PMID: 23974870 Van Goor F et al. Effect of ivacaftor on CFTR forms with missense mutations associated with defects in protein processing or function. J Cyst Fibros. 2014 13(1):29-36. PMID: 23891399

Comment:

The p.N1303K pathogenic mutation (also known as c.3909C>G), located in coding exon 24 of the CFTR gene, results from a C to G substitution at nucleotide position 3909. The asparagine at codon 1303 is replaced by lysine, an amino acid with similar properties. In one study, this mutation was identified in 216 cystic fibrosis alleles, including 10 homozygous individuals with elevated sweat chloride levels and decreased lung function. Of the 6 homozygous individuals with reported pancreatic status, all were pancreatic insufficient (Osborne L et al. Hum. Genet., 1992 Aug;89:653-8). In vitro functional studies determined that this mutation prevents the maturation, trafficking, and subsequent activity of the CFTR protein (Gregory RJ et al. Mol. Cell. Biol., 1991 Aug;11:3886-93). This pathogenic mutation is associated with elevated sweat chloride levels, decreased lung function, and pancreatic insufficiency; in vitro functional studies showed this mutation results in significantly reduced chloride conductance (Sosnay PR et al. Nat. Genet., 2013 Oct;45:1160-7). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

Comment:

The CFTR c.3909C>G variant is predicted to result in the amino acid substitution p.Asn1303Lys. This variant has been reported to be causative for cystic fibrosis (Sosnay et al. 2013. PubMed ID: 23974870; Masson et al. 2013. PubMed ID: 23951356; Osborne et al. 1991. PubMed ID: 1998343; Watson et al. 2004. PubMed ID: 15371902). This variant is reported in 0.058% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. This variant is interpreted as pathogenic.

Comment:

Variant interpretted as pathogenic and reported on 03/20/2016 by GTR ID 500068. 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.

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
Cystic Fibrosis.	Adam MP	-	2024	PMID: 20301428
Screening by single-molecule molecular inversion probes targeted sequencing panel of candidate genes of infertility in azoospermic infertile Jordanian males.	Batiha O	Human fertility (Cambridge, England)	2022	PMID: 34190021
The genetic structure of the Turkish population reveals high levels of variation and admixture.	Kars ME	Proceedings of the National Academy of Sciences of the United States of America	2021	PMID: 34426522
Analysis of CFTR Mutation Spectrum in Ethnic Russian Cystic Fibrosis Patients.	Petrova NV	Genes	2020	PMID: 32429104
Generation of an induced pluripotent stem cell line (MHHi018-A) from a patient with Cystic Fibrosis carrying p.Asn1303Lys (N1303K) mutation.	Merkert S	Stem cell research	2020	PMID: 32220772
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
Cystic Fibrosis Mutation Spectrum in North Macedonia: A Step Toward Personalized Therapy.	Terzic M	Balkan journal of medical genetics : BJMG	2019	PMID: 31523618
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
Secondary actionable findings identified by exome sequencing: expected impact on the organisation of care from the study of 700 consecutive tests.	Thauvin-Robinet C	European journal of human genetics : EJHG	2019	PMID: 31019283
Contribution of next generation sequencing in pediatric practice in Lebanon. A Study on 213 cases.	Nair P	Molecular genetics & genomic medicine	2018	PMID: 30293248
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
Complexity of phenotypes induced by p.Asn1303Lys-CFTR correlates with difficulty to rescue and activate this protein.	Farhat R	Cellular and molecular biology (Noisy-le-Grand, France)	2017	PMID: 29208182
Stabilization of a nucleotide-binding domain of the cystic fibrosis transmembrane conductance regulator yields insight into disease-causing mutations.	Vernon RM	The Journal of biological chemistry	2017	PMID: 28655774
From CFTR biology toward combinatorial pharmacotherapy: expanded classification of cystic fibrosis mutations.	Veit G	Molecular biology of the cell	2016	PMID: 26823392
Distribution of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutations in a Cohort of Patients Residing in Palestine.	Siryani I	PloS one	2015	PMID: 26208274
N1303K (c.3909C>G) mutation and splicing: implication of its c.[744-33GATT(6); 869+11C>T] complex allele in CFTR exon 7 aberrant splicing.	Farhat R	BioMed research international	2015	PMID: 26075213
Rescue of NBD2 mutants N1303K and S1235R of CFTR by small-molecule correctors and transcomplementation.	Rapino D	PloS one	2015	PMID: 25799511
Missense variants in CFTR nucleotide-binding domains predict quantitative phenotypes associated with cystic fibrosis disease severity.	Masica DL	Human molecular genetics	2015	PMID: 25489051
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
The relative frequency of CFTR mutation classes in European patients with cystic fibrosis.	De Boeck K	Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society	2014	PMID: 24440181
Effect of ivacaftor on CFTR forms with missense mutations associated with defects in protein processing or function.	Van Goor F	Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society	2014	PMID: 23891399
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
Clinical and morphological characteristics of sporadic genetically determined pancreatitis as compared to idiopathic pancreatitis: higher risk of pancreatic cancer in CFTR variants.	Hamoir C	Digestion	2013	PMID: 23751316
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
Extensive molecular analysis of patients bearing CFTR-related disorders.	Amato F	The Journal of molecular diagnostics : JMD	2012	PMID: 22020151
Enhanced frequency of CFTR gene variants in couples who are candidates for assisted reproductive technology treatment.	Tomaiuolo R	Clinical chemistry and laboratory medicine	2011	PMID: 21679131
Common CFTR haplotypes and susceptibility to chronic pancreatitis and congenital bilateral absence of the vas deferens.	Steiner B	Human mutation	2011	PMID: 21520337
Carrier testing for severe childhood recessive diseases by next-generation sequencing.	Bell CJ	Science translational medicine	2011	PMID: 21228398
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
Bilateral spontaneous pneumothorax in a newborn with N1303K mutation of cystic fibrosis (CFTR) gene.	Ataseven F	Tuberkuloz ve toraks	2010	PMID: 20865572
Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and risk for pancreatic adenocarcinoma.	McWilliams RR	Cancer	2010	PMID: 19885835
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
N1303K and IVS8-5T, clinical presentation within a family with atypical cystic fibrosis.	Van Hoorenbeeck K	Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society	2007	PMID: 17127107
[3120+1kbdel8.6kb]+[p.N1303K] genotype in an Emirati cystic fibrosis patient: indication of a founder mutation in Palestinian Arabs.	Saleheen D	Journal of Ayub Medical College, Abbottabad : JAMC	2006	PMID: 17348320
Genotype-phenotype correlation for pulmonary function in cystic fibrosis.	de Gracia J	Thorax	2005	PMID: 15994263
Segregation analysis in cystic fibrosis at-risk family demonstrates that the M348K CFTR mutation is a rare innocuous polymorphism.	D'Apice MR	Prenatal diagnosis	2004	PMID: 15614862
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
Pseudo-Bartter's syndrome in an Egyptian infant with cystic fibrosis mutation N1303K.	Wahab AA	Journal of tropical pediatrics	2004	PMID: 15357568
Effect of genotype on phenotype and mortality in cystic fibrosis: a retrospective cohort study.	McKone EF	Lancet (London, England)	2003	PMID: 12767731
XV-2c/KM-19 haplotype analysis of cystic fibrosis mutations in Mexican patients.	Orozco L	American journal of medical genetics	2001	PMID: 11484207
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
Frequency and clinical significance of the S1235R mutation in the cystic fibrosis transmembrane conductance regulator gene: results from a collaborative study.	Monaghan KG	American journal of medical genetics	2000	PMID: 11186891
Geographic distribution of cystic fibrosis transmembrane regulator gene mutations in Saudi Arabia.	Banjar H	Eastern Mediterranean health journal = La revue de sante de la Mediterranee orientale = al-Majallah al-sihhiyah li-sharq al-mutawassit	1999	PMID: 11924117
Incidence and expression of the N1303K mutation of the cystic fibrosis (CFTR) gene.	Osborne L	Human genetics	1992	PMID: 1380943
A mutation in the second nucleotide binding fold of the cystic fibrosis gene.	Osborne L	American journal of human genetics	1991	PMID: 1998343
Nine mutations in the cystic fibrosis (CF) gene account for 80% of the CF chromosomes in French patients.	Simon-Bouy B	Clinical genetics	1991	PMID: 1723032
Maturation and function of cystic fibrosis transmembrane conductance regulator variants bearing mutations in putative nucleotide-binding domains 1 and 2.	Gregory RJ	Molecular and cellular biology	1991	PMID: 1712898
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CFTR	-	-	-	-
https://cftr2.org	-	-	-	-
https://cftr2.org/	-	-	-	-
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Text-mined citations for rs80034486 ...

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 10, 2024

ClinVar Genomic variation as it relates to human health

NM_000492.4(CFTR):c.3909C>G (p.Asn1303Lys)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs80034486 ...