NM_000492.4(CFTR):c.3908A>T (p.Asn1303Ile) AND CFTR-related disorder

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Oct 7, 2025
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001009506.2

Allele description [Variation Report for NM_000492.4(CFTR):c.3908A>T (p.Asn1303Ile)]

NM_000492.4(CFTR):c.3908A>T (p.Asn1303Ile)

Gene:

CFTR:CF transmembrane conductance regulator [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q31.2

Genomic location:

Preferred name:

NM_000492.4(CFTR):c.3908A>T (p.Asn1303Ile)

HGVS:

NC_000007.14:g.117652876A>T
NG_016465.4:g.192093A>T
NM_000492.4:c.3908A>TMANE SELECT
NP_000483.3:p.Asn1303Ile
NP_000483.3:p.Asn1303Ile
LRG_663t1:c.3908A>T
LRG_663:g.192093A>T
LRG_663p1:p.Asn1303Ile
NC_000007.13:g.117292930A>T
NM_000492.3:c.3908A>T

Protein change:

N1303I

Links:

dbSNP: rs397508636

Molecular consequence:

NM_000492.4:c.3908A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: CFTR-related disorder (CFTR-RD)
Synonyms:: CFTR-related disorders; CFTR-related condition
Identifiers:: MONDO: MONDO:7770004; MedGen: C5924204

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001169601	CFTR-France	criteria provided, single submitter (Claustres M et al. (Hum Mutat 2017))	Pathogenic (Mar 26, 2018)	germline	curation	PubMed (1) [See all records that cite this PMID]
SCV007536810	Natera, Inc.	criteria provided, single submitter (Natera Variant Classification Schema (03/2026))	Likely pathogenic (Oct 7, 2025)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 39482189, 38388235 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001169601

CFTR-France

criteria provided, single submitter

(Claustres M et al. (Hum Mutat 2017))

Pathogenic
(Mar 26, 2018)

germline

curation

PubMed (1)
[See all records that cite this PMID]

SCV007536810

Natera, Inc.

criteria provided, single submitter

(Natera Variant Classification Schema (03/2026))

Likely pathogenic
(Oct 7, 2025)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

CFTR-France, a national relational patient database for sharing genetic and phenotypic data associated with rare CFTR variants.

Claustres M, Thèze C, des Georges M, Baux D, Girodon E, Bienvenu T, Audrezet MP, Dugueperoux I, Férec C, Lalau G, Pagin A, Kitzis A, Thoreau V, Gaston V, Bieth E, Malinge MC, Reboul MP, Fergelot P, Lemonnier L, Mekki C, Fanen P, Bergougnoux A, et al.

Hum Mutat. 2017 Oct;38(10):1297-1315. doi: 10.1002/humu.23276. Epub 2017 Jun 28.

PubMed [citation]

PMID:: 28603918

Pseudo-Bartter syndrome: A CFTR-related disorder?

Rodriguez Mier N, Antoons V, Cuyx S, Santo Ramalho A, Boon M, Proesmans M, Mekahli D, Vermeulen F.

J Cyst Fibros. 2025 Mar;24(2):401-403. doi: 10.1016/j.jcf.2024.10.007. Epub 2024 Oct 31.

PubMed [citation]

PMID:: 39482189

See all PubMed Citations (3)

Details of each submission

From CFTR-France, SCV001169601.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Natera, Inc., SCV007536810.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The c.3908A>T variant in CFTR is a missense variant predicted to cause substitution of asparagine to isoleucine at amino acid 1303. This variant is rare in the general population with a frequency below the threshold expected for the associated phenotype(s). This variant has been observed in one or more individuals affected with the associated recessive disease, as either homozygous or compound heterozygous with a second variant (PMID: 39482189). Functional studies show that this variant may disrupt protein function (PMID: 38388235). A different variant at the same position has been determined to be Pathogenic or Likely Pathogenic. Computational prediction algorithms indicate this variant is likely to affect gene or protein function. Given the available evidence, this variant is classified as Likely Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Aug 4, 2026

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