NM_000492.4(CFTR):c.1352G>T (p.Gly451Val) AND Cystic fibrosis

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Sep 15, 2025
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000669047.3

Allele description [Variation Report for NM_000492.4(CFTR):c.1352G>T (p.Gly451Val)]

NM_000492.4(CFTR):c.1352G>T (p.Gly451Val)

Genes:

CFTR:CF transmembrane conductance regulator [Gene - OMIM - HGNC]
CFTR-AS1:CFTR antisense RNA 1 [Gene - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q31.2

Genomic location:

Preferred name:

NM_000492.4(CFTR):c.1352G>T (p.Gly451Val)

HGVS:

NC_000007.14:g.117548783G>T
NG_016465.4:g.88000G>T
NM_000492.4:c.1352G>TMANE SELECT
NP_000483.3:p.Gly451Val
NP_000483.3:p.Gly451Val
LRG_663t1:c.1352G>T
LRG_663:g.88000G>T
LRG_663p1:p.Gly451Val
NC_000007.13:g.117188837G>T
NM_000492.3:c.1352G>T

Protein change:

G451V

Links:

dbSNP: rs1554382653

Molecular consequence:

NM_000492.4:c.1352G>T - 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
SCV000793746	Counsyl	no assertion criteria provided	Uncertain significance (Aug 30, 2017)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005204831	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Sep 15, 2025)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 16189704, 32429104, 30763667, 35698092, 35858753, 38388235, 34613844, 37701179 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000793746

Counsyl

no assertion criteria provided

Uncertain significance
(Aug 30, 2017)

unknown

clinical testing

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

SCV005204831

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Sep 15, 2025)

germline

clinical testing

PubMed (8)
[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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Extensive sequencing of the CFTR gene: lessons learned from the first 157 patient samples.

McGinniss MJ, Chen C, Redman JB, Buller A, Quan F, Peng M, Giusti R, Hantash FM, Huang D, Sun W, Strom CM.

Hum Genet. 2005 Dec;118(3-4):331-8. Epub 2005 Sep 28.

PubMed [citation]

PMID:: 16189704

Analysis of CFTR Mutation Spectrum in Ethnic Russian Cystic Fibrosis Patients.

Petrova NV, Kashirskaya NY, Vasilyeva TA, Kondratyeva EI, Zhekaite EK, Voronkova AY, Sherman VD, Galkina VA, Ginter EK, Kutsev SI, Marakhonov AV, Zinchenko RA.

Genes (Basel). 2020 May 15;11(5). doi: 10.3390/genes11050554.

PubMed [citation]

PMID:: 32429104
PMCID:: PMC7288340

See all PubMed Citations (8)

Details of each submission

From Counsyl, SCV000793746.2

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

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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005204831.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

Variant summary: CFTR c.1352G>T (p.Gly451Val) results in a non-conservative amino acid change located in the ABC transporter-like, ATP-binding domain (IPR003439) 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 244264 control chromosomes. c.1352G>T has been observed in heterozygous, presumed compound heterozygous, and complex presumed compound heterozygous (sharing an allele with another rare VUS p.Gly253Arg) states in multiple individuals affected with Cystic Fibrosis and/or CFTR-related conditions (example: McGinness_2005, Petrova_2020, Rueda-Nieto_2022, Ruiz-Cabezas_2019, Shen_2022, Woodall_2021, Woodall_2023). The impact of the complex allele consisting of c.[757G>A;1352G>T] p.[(Gly253Arg;Gly451Val)] may be pathogenic as it has been seen in several individuals affected with cystic fibrosis-spectrum disease with various presumed compound heterozygous pathogenic variants on the second allele (example: Ruiz-Cabezas_2019); however, the impact of p.Gly451Val alone cannot be disambiguated. These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect resulted in approximately 16.37% of normal chloride channel conductance relative to wild type (example: Bihler_2024). The following publications have been ascertained in the context of this evaluation (PMID: 16189704, 32429104, 30763667, 35698092, 35858753, 34613844, 37701179, 38388235). ClinVar contains an entry for this variant (Variation ID: 553569). Based on the evidence outlined above, the variant was 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: Dec 14, 2025

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