NM_000492.4(CFTR):c.223C>T (p.Arg75Ter) AND not provided

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Nov 20, 2023
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:: RCV001284476.19

Allele description [Variation Report for NM_000492.4(CFTR):c.223C>T (p.Arg75Ter)]

NM_000492.4(CFTR):c.223C>T (p.Arg75Ter)

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.223C>T (p.Arg75Ter)

Other names:

p.Arg75*

HGVS:

NC_000007.14:g.117509092C>T
NG_016465.4:g.48309C>T
NG_062452.1:g.730C>T
NM_000492.4:c.223C>TMANE SELECT
NP_000483.3:p.Arg75Ter
NP_000483.3:p.Arg75Ter
LRG_663t1:c.223C>T
LRG_663:g.48309C>T
LRG_663p1:p.Arg75Ter
NC_000007.13:g.117149146C>T
NM_000492.3:c.223C>T
p.Arg75X

Protein change:

R75*

Links:

Genetic Testing Registry (GTR): GTR000074114; dbSNP: rs121908749

NCBI 1000 Genomes Browser:

rs121908749

Molecular consequence:

NM_000492.4:c.223C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001470291	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Oct 16, 2019)	unknown	clinical testing	PubMed (9) [See all records that cite these PMIDs] 7525450, 9806422, 22658665, 22975760, 23974870, 23420618, 15858154, 11668613, 26467025
SCV001474367	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	Pathogenic (Nov 20, 2023)	germline	clinical testing	Citation Link,
SCV002019235	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 22, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005046905	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 9, 2022)	germline	clinical testing	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	1	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

Detection of more than 50 different CFTR mutations in a large group of German cystic fibrosis patients.

Dörk T, Mekus F, Schmidt K, Bosshammer J, Fislage R, Heuer T, Dziadek V, Neumann T, Kälin N, Wulbrand U, et al.

Hum Genet. 1994 Nov;94(5):533-42.

PubMed [citation]

PMID:: 7525450

The association of nonsense codons with exon skipping.

Valentine CR.

Mutat Res. 1998 Sep;411(2):87-117. Review.

PubMed [citation]

PMID:: 9806422

See all PubMed Citations (10)

Details of each submission

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV001470291.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and not found in general population data.

#	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 ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001474367.2

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

Description

The CFTR c.223C>T; p.Arg75Ter variant (rs121908749) is reported in the literature in individuals affected with cystic fibrosis (Dork 1994, Sosnay 2013, CFTR2 database). This variant has been observed in affected individuals in trans to another pathogenic variant (Dork 1994) and the majority of patients described exhibit elevated sweat chloride and pancreatic insufficiency (Sosnay 2013, CFTR2 database). This variant is found on only six chromosomes (6/250976 alleles) in the Genome Aggregation Database (v2.1.1), indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: CFTR2 database: https://cftr2.org Dork T et al. Detection of more than 50 different CFTR mutations in a large group of German cystic fibrosis patients. Hum Genet. 1994 Nov;94(5):533-42. Sosnay PR et al. Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. Nat Genet. 2013 Oct;45(10):1160-7.

#	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 Revvity Omics, Revvity, SCV002019235.3

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Mayo Clinic Laboratories, Mayo Clinic, SCV005046905.1

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

Last Updated: Sep 16, 2024

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