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NM_000492.4(CFTR):c.1054C>T (p.Arg352Trp)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(1);Likely pathogenic(1);Uncertain significance(5)

Review status:
criteria provided, conflicting interpretations
Submissions:
7 (Most recent: Sep 1, 2021)
Last evaluated:
Jul 22, 2021
Accession:
VCV000035816.13
Variation ID:
35816
Description:
single nucleotide variant
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NM_000492.4(CFTR):c.1054C>T (p.Arg352Trp)

Allele ID
44480
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
7q31.2
Genomic location
7: 117540284 (GRCh38) GRCh38 UCSC
7: 117180338 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_663:g.79501C>T
LRG_663t1:c.1054C>T LRG_663p1:p.Arg352Trp
NC_000007.14:g.117540284C>T
... more HGVS
Protein change
R352W
Other names
-
Canonical SPDI
NC_000007.14:117540283:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
0.00020 (T)

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00010
The Genome Aggregation Database (gnomAD) 0.00007
Trans-Omics for Precision Medicine (TOPMed) 0.00021
Trans-Omics for Precision Medicine (TOPMed) 0.00018
1000 Genomes Project 0.00020
The Genome Aggregation Database (gnomAD), exomes 0.00041
Exome Aggregation Consortium (ExAC) 0.00047
Links
ClinGen: CA325686
dbSNP: rs193922497
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 2 criteria provided, multiple submitters, no conflicts Oct 31, 2019 RCV000727191.4
Conflicting interpretations of pathogenicity 3 criteria provided, conflicting interpretations Jul 22, 2021 RCV000029469.14
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Mar 23, 2021 RCV000506190.7
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
CFTR - - GRCh38
GRCh37
1974 2730

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Dec 10, 2018)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000603070.3
Submitted: (Aug 05, 2019)
Evidence details
Comment:
The CFTR c.1054C>T; p.Arg352Trp variant (rs193922497) is reported in individuals with cystic fibrosis (CF) (Schrijver 2005), mildly elevated sweat chloride (McGinniss 2005), and congenital absence … (more)
Uncertain significance
(Oct 31, 2019)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: unknown
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000601037.2
Submitted: (Dec 31, 2020)
Evidence details
Publications
PubMed (8)
Uncertain significance
(Mar 23, 2021)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000052119.3
Submitted: (Apr 07, 2021)
Evidence details
Publications
PubMed (16)
Comment:
Variant summary: CFTR c.1054C>T (p.Arg352Trp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging … (more)
Likely benign
(Nov 25, 2020)
criteria provided, single submitter
Method: clinical testing
Cystic fibrosis
Allele origin: germline
Invitae
Accession: SCV000074226.8
Submitted: (Jan 07, 2021)
Evidence details
Uncertain significance
(Mar 08, 2017)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000706515.2
Submitted: (Sep 19, 2018)
Evidence details
Other databases
http://www.egl-eurofins.com/emvc…
Uncertain significance
(Nov 06, 2018)
criteria provided, single submitter
Method: clinical testing
CFTR-Related Disorders
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV000916179.1
Submitted: (Feb 01, 2019)
Evidence details
Publications
PubMed (4)
Comment:
The CFTR c.1054C>T (p.Arg352Trp) variant is a missense variant that has been reported in at least four studies, in which it is found in a … (more)
Uncertain significance
(Jul 22, 2021)
criteria provided, single submitter
Method: clinical testing
Cystic fibrosis
Allele origin: germline
Nilou-Genome Lab
Accession: SCV001822035.1
Submitted: (Sep 01, 2021)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Correlating Cystic Fibrosis Transmembrane Conductance Regulator Function with Clinical Features to Inform Precision Treatment of Cystic Fibrosis. McCague AF American journal of respiratory and critical care medicine 2019 PMID: 30888834
Functional Assays Are Essential for Interpretation of Missense Variants Associated with Variable Expressivity. Raraigh KS American journal of human genetics 2018 PMID: 29805046
Sweat chloride and immunoreactive trypsinogen in infants carrying two <i>CFTR</i> mutations and not affected by cystic fibrosis. Castellani C Archives of disease in childhood 2017 PMID: 26755536
Targeted mutation screening panels expose systematic population bias in detection of cystic fibrosis risk. Lim RM Genetics in medicine : official journal of the American College of Medical Genetics 2016 PMID: 25880441
Newborn Screening for Cystic Fibrosis in California. Kharrazi M Pediatrics 2015 PMID: 26574590
Carrier testing for severe childhood recessive diseases by next-generation sequencing. Bell CJ Science translational medicine 2011 PMID: 21228398
Newborn screening for cystic fibrosis in Alberta: Two years of experience. Lilley M Paediatrics & child health 2010 PMID: 22043142
A 10-year large-scale cystic fibrosis carrier screening in the Italian population. Picci L Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society 2010 PMID: 19897426
Sweat chloride testing in infants identified as heterozygote carriers by newborn screening. Soultan ZN The Journal of pediatrics 2008 PMID: 19014821
Mutations at arginine 352 alter the pore architecture of CFTR. Cui G The Journal of membrane biology 2008 PMID: 18421494
New York State cystic fibrosis consortium: the first 2.5 years of experience with cystic fibrosis newborn screening in an ethnically diverse population. Giusti R Pediatrics 2007 PMID: 17272608
Highly preferential association of NonF508del CF mutations with the M470 allele. Ciminelli BM Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society 2007 PMID: 16784904
Extensive sequencing of the CFTR gene: lessons learned from the first 157 patient samples. McGinniss MJ Human genetics 2005 PMID: 16189704
Gender-sensitive association of CFTR gene mutations and 5T allele emerging from a large survey on infertility. Morea A Molecular human reproduction 2005 PMID: 16126774
Diagnostic testing by CFTR gene mutation analysis in a large group of Hispanics: novel mutations and assessment of a population-specific mutation spectrum. Schrijver I The Journal of molecular diagnostics : JMD 2005 PMID: 15858154
Cystic fibrosis in Greece: molecular diagnosis, haplotypes, prenatal diagnosis and carrier identification amongst high-risk individuals. Kanavakis E Clinical genetics 2003 PMID: 12752573
A combined analysis of the cystic fibrosis transmembrane conductance regulator: implications for structure and disease models. Chen JM Molecular biology and evolution 2001 PMID: 11504857
Arg352 is a major determinant of charge selectivity in the cystic fibrosis transmembrane conductance regulator chloride channel. Guinamard R Biochemistry 1999 PMID: 10220340
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CFTR - - - -

Text-mined citations for rs193922497...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 27, 2021