NM_000492.4(CFTR):c.3925C>T (p.Gln1309Ter) AND Cystic fibrosis

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Sep 5, 2022
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:: RCV000757842.8

Allele description [Variation Report for NM_000492.4(CFTR):c.3925C>T (p.Gln1309Ter)]

NM_000492.4(CFTR):c.3925C>T (p.Gln1309Ter)

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.3925C>T (p.Gln1309Ter)

Other names:

Q1309X

HGVS:

NC_000007.14:g.117652893C>T
NG_016465.4:g.192110C>T
NM_000492.4:c.3925C>TMANE SELECT
NP_000483.3:p.Gln1309Ter
LRG_663t1:c.3925C>T
LRG_663:g.192110C>T
NC_000007.13:g.117292947C>T
NM_000492.3:c.3925C>T

Protein change:

Q1309*

Links:

dbSNP: rs193922732

NCBI 1000 Genomes Browser:

rs193922732

Molecular consequence:

NM_000492.4:c.3925C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

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

Recent activity

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PREDICTED: Homo sapiens cilia and flagella associated protein 52 (CFAP52), trans...
PREDICTED: Homo sapiens cilia and flagella associated protein 52 (CFAP52), transcript variant X3, mRNA
gi|2217310171|ref|XM_047435439.1|

Nucleotide
Arabidopsis thaliana Zn-dependent exopeptidases superfamily protein (AT5G20660),...
Arabidopsis thaliana Zn-dependent exopeptidases superfamily protein (AT5G20660), mRNA
gi|238481328|ref|NM_001161255.1|

Nucleotide
SRX20904115 (1)
SRA
Bulbophyllum ruginosum isolate FS5885_OR1400 atpH-atpI intergenic spacer, partia...
Bulbophyllum ruginosum isolate FS5885_OR1400 atpH-atpI intergenic spacer, partial sequence; and ATP synthase (atpI) gene, partial cds; chloroplast
gi|927091737|gb|KJ559017.1|

Nucleotide
Oryza sequence.
Oryza sequence.
PopSet: 169880349

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000886336	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Pathogenic (Nov 5, 2018)	unknown	clinical testing	Citation Link,
SCV001381191	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 23, 2019)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 1695717, 7691345, 9725922, 28492532
SCV002573902	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 5, 2022)	unknown	curation	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000886336

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2017)

Pathogenic
(Nov 5, 2018)

unknown

clinical testing

Citation Link,

SCV001381191

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 23, 2019)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV002573902

Institute of Human Genetics, University of Leipzig Medical Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Sep 5, 2022)

unknown

curation

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

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	yes	3	not provided	not provided	not provided	not provided	clinical testing, curation

Citations

PubMed

A cluster of cystic fibrosis mutations in the first nucleotide-binding fold of the cystic fibrosis conductance regulator protein.

Cutting GR, Kasch LM, Rosenstein BJ, Zielenski J, Tsui LC, Antonarakis SE, Kazazian HH Jr.

Nature. 1990 Jul 26;346(6282):366-9.

PubMed [citation]

PMID:: 1695717

Molecular basis of defective anion transport in L cells expressing recombinant forms of CFTR.

Yang Y, Devor DC, Engelhardt JF, Ernst SA, Strong TV, Collins FS, Cohn JA, Frizzell RA, Wilson JM.

Hum Mol Genet. 1993 Aug;2(8):1253-61.

PubMed [citation]

PMID:: 7691345

See all PubMed Citations (5)

Details of each submission

From Mendelics, SCV000886336.2

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

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001381191.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

Loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with CFTR-related conditions. ClinVar contains an entry for this variant (Variation ID: 618939). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln1309*) in the CFTR gene. It is expected to result in an absent or disrupted protein product.

#	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 Institute of Human Genetics, University of Leipzig Medical Center, SCV002573902.1

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

Description

This variant was identified in 3 unrelated patients with a clinically confirmed diagnosis of cystic fibrosis. The variant was classified in the context of a project re-classifying variants in the German Cystic Fibrosis Registry (Muko.e.V.). Link: https://www.muko.info/angebote/qualitaetsmanagement/register/cf-einrichtungen/mukoweb. Criteria applied: PVS1, PM2_SUP, PP4

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		3	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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