NM_000492.4(CFTR):c.3877G>A (p.Val1293Ile) AND Cystic fibrosis

Germline classification:: Uncertain significance (4 submissions)
Last evaluated:: Apr 3, 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:: RCV000667886.13

Allele description [Variation Report for NM_000492.4(CFTR):c.3877G>A (p.Val1293Ile)]

NM_000492.4(CFTR):c.3877G>A (p.Val1293Ile)

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.3877G>A (p.Val1293Ile)

HGVS:

NC_000007.14:g.117652845G>A
NG_016465.4:g.192062G>A
NM_000492.4:c.3877G>AMANE SELECT
NP_000483.3:p.Val1293Ile
NP_000483.3:p.Val1293Ile
LRG_663t1:c.3877G>A
LRG_663:g.192062G>A
LRG_663p1:p.Val1293Ile
NC_000007.13:g.117292899G>A
NM_000492.3:c.3877G>A
NM_000492.4:c.3877G>A

Protein change:

V1293I

Links:

dbSNP: rs769931559

Molecular consequence:

NM_000492.4:c.3877G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cystic fibrosis (CF)
Synonyms:: MUCOVISCIDOSIS
Identifiers:: MONDO: MONDO:0009061; MedGen: C0010674; Orphanet: 586; OMIM: 219700

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000792398	Counsyl	no assertion criteria provided	Uncertain significance (Jun 27, 2017)	unknown	clinical testing
SCV001421825	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 3, 2025)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 12815607, 28040058, 28492532
SCV002027522	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 5, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002624882	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jul 8, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 11379874, 28040058 Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Comparison of the CFTR mutation spectrum in three cohorts of patients of Celtic origin from Brittany (France) and Ireland.

Scotet V, Barton DE, Watson JB, Audrézet MP, McDevitt T, McQuaid S, Shortt C, De Braekeleer M, Férec C, Le Maréchal C.

Hum Mutat. 2003 Jul;22(1):105.

PubMed [citation]

PMID:: 12815607

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9..

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

See all PubMed Citations (5)

Details of each submission

From Counsyl, SCV000792398.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com.

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001421825.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1293 of the CFTR protein (p.Val1293Ile). This variant is present in population databases (rs769931559, gnomAD 0.004%). This missense change has been observed in individual(s) with cystic fibrosis (PMID: 12815607, 28040058). ClinVar contains an entry for this variant (Variation ID: 552594). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt CFTR protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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

From Genome-Nilou Lab, SCV002027522.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Ambry Genetics, SCV002624882.3

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

Description

The p.V1293I variant (also known as c.3877G>A), located in coding exon 24 of the CFTR gene, results from a G to A substitution at nucleotide position 3877. The valine at codon 1293 is replaced by isoleucine, an amino acid with highly similar properties. This variant was identified in a cystic fibrosis cohort with no second CFTR varaint and in a control sample (El-Seedy A et al. Cell. Mol. Biol. (Noisy-le-grand), 2016 Nov;62:21-28; Le Maréchal C et al. Hum. Genet., 2001 Apr;108:290-8). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

#	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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