VCV000053665.9 - ClinVar

NM_000492.4(CFTR):c.314T>A (p.Ile105Asn)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Pathogenic/Likely pathogenic

3 out of 4 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000492.4(CFTR):c.314T>A (p.Ile105Asn)

Variation ID: 53665 Accession: VCV000053665.9

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 7q31.2 7: 117530939 (GRCh38) [ NCBI UCSC ] 7: 117170993 (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	May 10, 2021	Feb 7, 2026	Aug 12, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_000492.4:c.314T>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000483.3:p.Ile105Asn	missense
NC_000007.14:g.117530939T>A
NC_000007.13:g.117170993T>A
NG_016465.4:g.70156T>A
LRG_663:g.70156T>A
LRG_663t1:c.314T>A	LRG_663p1:p.Ile105Asn

... more HGVS ... less HGVS

Protein change

I105N

Other names

Canonical SPDI

NC_000007.14:117530938:T:A

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.

Links

ClinGen: CA327065 dbSNP: rs397508509 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		Gene associated with autosomal recessive phenotype	Not yet evaluated	GRCh38 GRCh37	3771	6170

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 (2)	criteria provided, multiple submitters, no conflicts	Aug 12, 2025	RCV001382997.8
CFTR-related disorder	Pathogenic (1)	no assertion criteria provided	Sep 1, 2017	RCV001826657.1
Bronchiectasis with or without elevated sweat chloride 1 Congenital bilateral aplasia of vas deferens from CFTR mutation Cystic fibrosis Hereditary pancreatitis	Likely pathogenic (1)	criteria provided, single submitter	Apr 13, 2024	RCV005042143.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely pathogenic (Apr 13, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Hereditary pancreatitis Bronchiectasis with or without elevated sweat chloride 1 Cystic fibrosis Congenital bilateral aplasia of vas deferens from CFTR mutation Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.	Fulgent Genetics, Fulgent Genetics Accession: SCV005666792.1 First in ClinVar: Jan 25, 2025 Last updated: Jan 25, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (May 08, 2024) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Cystic fibrosis	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001581993.5 First in ClinVar: May 10, 2021 Last updated: Feb 16, 2025	Publications: PubMed (4) PubMed: 25697318‚ 26574590‚ 27214204‚ 28830496 Comment: show This sequence change replaces isoleucine, which is neutral and non-polar, with asparagine, which is neutral and polar, at codon 105 of the CFTR protein (p.Ile105Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with cystic fibrosis (PMID: 25697318, 26574590, 27214204, 28830496; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 53665). 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%. For these reasons, this variant has been classified as Pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Aug 12, 2025) C Contributing to aggregate classification	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Cystic fibrosis	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV005076731.2 First in ClinVar: Jul 15, 2024 Last updated: Feb 07, 2026	Publications: PubMed (6) PubMed: 19318346‚ 20657600‚ 25697318‚ 27214204‚ 28830496‚ 38388235 Comment: show Variant summary: CFTR c.314T>A (p.Ile105Asn) results in a non-conservative amino acid change located in the ABC transporter type 1, transmembrane domain (IPR011527) of the encoded protein sequence. Algorithms developed to predict the effect of missense changes on protein structure and function all suggest that this variant is likely to be disruptive. The variant was absent in 251142 control chromosomes. c.314T>A has been reported in the literature in multiple compound heterozygous individuals affected with Cystic Fibrosis or CBAVD (e.g. DeWatcher_2017, Goubau_2009, Guiliani_2010, Lay-son_2014, Salinas_2016, internal data).These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity (Bihler_2024). The following publications have been ascertained in the context of this evaluation (PMID: 28830496, 19318346, 20657600, 25697318, 27214204, 38388235). ClinVar contains an entry for this variant (Variation ID: 53665). Based on the evidence outlined above, the variant was classified as pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Sep 01, 2017) N Not contributing to aggregate classification	no assertion criteria provided	CFTR-related disorders	Natera, Inc. Accession: SCV002080118.1 First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

This sequence change replaces isoleucine, which is neutral and non-polar, with asparagine, which is neutral and polar, at codon 105 of the CFTR protein (p.Ile105Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with cystic fibrosis (PMID: 25697318, 26574590, 27214204, 28830496; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 53665). 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%. For these reasons, this variant has been classified as Pathogenic.

Comment:

Variant summary: CFTR c.314T>A (p.Ile105Asn) results in a non-conservative amino acid change located in the ABC transporter type 1, transmembrane domain (IPR011527) of the encoded protein sequence. Algorithms developed to predict the effect of missense changes on protein structure and function all suggest that this variant is likely to be disruptive. The variant was absent in 251142 control chromosomes. c.314T>A has been reported in the literature in multiple compound heterozygous individuals affected with Cystic Fibrosis or CBAVD (e.g. DeWatcher_2017, Goubau_2009, Guiliani_2010, Lay-son_2014, Salinas_2016, internal data).These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity (Bihler_2024). The following publications have been ascertained in the context of this evaluation (PMID: 28830496, 19318346, 20657600, 25697318, 27214204, 38388235). ClinVar contains an entry for this variant (Variation ID: 53665). Based on the evidence outlined above, the variant was classified as pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
In vitro modulator responsiveness of 655 CFTR variants found in people with cystic fibrosis.	Bihler H	Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society	2024	PMID: 38388235
What can the CF registry tell us about rare CFTR-mutations? A Belgian study.	De Wachter E	Orphanet journal of rare diseases	2017	PMID: 28830496
Benign and Deleterious Cystic Fibrosis Transmembrane Conductance Regulator Mutations Identified by Sequencing in Positive Cystic Fibrosis Newborn Screen Children from California.	Salinas DB	PloS one	2016	PMID: 27214204
Newborn Screening for Cystic Fibrosis in California.	Kharrazi M	Pediatrics	2015	PMID: 26574590
[CFTR gene sequencing in a group of Chilean patients with cystic fibrosis].	Lay-Son R G	Revista chilena de pediatria	2014	PMID: 25697318
Identification of the second CFTR mutation in patients with congenital bilateral absence of vas deferens undergoing ART protocols.	Giuliani R	Asian journal of andrology	2010	PMID: 20657600
Phenotypic characterisation of patients with intermediate sweat chloride values: towards validation of the European diagnostic algorithm for cystic fibrosis.	Goubau C	Thorax	2009	PMID: 19318346

Text-mined citations for rs397508509 ...

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 Feb 08, 2026