ClinVar Genomic variation as it relates to human health
NM_000492.4(CFTR):c.1679G>C (p.Arg560Thr)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000492.4(CFTR):c.1679G>C (p.Arg560Thr)
Variation ID: 7113 Accession: VCV000007113.124
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7q31.2 7: 117587833 (GRCh38) [ NCBI UCSC ] 7: 117227887 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Mar 29, 2015 May 1, 2024 Mar 3, 2004 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000492.4:c.1679G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000483.3:p.Arg560Thr missense NC_000007.14:g.117587833G>C NC_000007.13:g.117227887G>C NG_016465.4:g.127050G>C NG_056131.3:g.788G>C LRG_663:g.127050G>C LRG_663t1:c.1679G>C LRG_663p1:p.Arg560Thr P13569:p.Arg560Thr - Protein change
- R560T
- Other names
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- Canonical SPDI
- NC_000007.14:117587832:G:C
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00003
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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CFTR | - | - |
GRCh38 GRCh37 |
3704 | 5025 | |
LOC111674475 | - | - | - | GRCh38 | - | 139 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (9) |
practice guideline
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Mar 3, 2004 | RCV000007533.34 | |
Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Aug 28, 2020 | RCV000224789.22 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 13, 2018 | RCV000780134.9 | |
Pathogenic (1) |
criteria provided, single submitter
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- | RCV001004262.9 | |
CFTR-related disorder
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Pathogenic (3) |
criteria provided, single submitter
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Sep 23, 2022 | RCV001831521.13 |
Pathogenic (1) |
criteria provided, single submitter
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Oct 25, 2021 | RCV002504762.8 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 28, 2023 | RCV003473005.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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pathogenic
(Mar 03, 2004)
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practice guideline
Method: curation
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Cystic fibrosis
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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American College of Medical Genetics and Genomics (ACMG)
Study: The ACMG recommended carrier screening panel
Accession: SCV000071397.2 First in ClinVar: Jun 04, 2013 Last updated: Mar 29, 2015 |
Comment:
Converted during submission to Pathogenic.
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Pathogenic
(Mar 17, 2017)
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reviewed by expert panel
Method: research
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Cystic fibrosis
Affected status: yes
Allele origin:
germline
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CFTR2
Study: CFTR2
Accession: SCV000071524.4 First in ClinVar: Oct 18, 2013 Last updated: Oct 11, 2015 |
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Pathogenic
(Mar 13, 2018)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000917179.1
First in ClinVar: Jun 03, 2019 Last updated: Jun 03, 2019 |
Comment:
Variant summary: CFTR c.1679G>C (p.Arg560Thr) results in a non-conservative amino acid change located in the ABC transporter-like and AAA+ ATPase domains of the encoded protein … (more)
Variant summary: CFTR c.1679G>C (p.Arg560Thr) results in a non-conservative amino acid change located in the ABC transporter-like and AAA+ ATPase domains of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. Several computational tools predict a significant impact on normal splicing: four predict the variant abolishes a 5' splicing donor site. These splicing predictions have yet to be confirmed by functional studies, however studies assessing the variant effect at the protein level have shown a defective glycosylation/maturation and chloride conductance (Van Goor 2013, Sosnay 2013). The variant allele was found at a frequency of 1.7e-05 in 293912 control chromosomes. The c.1679G>C variant has been reported in the literature in numerous individuals affected with Classic Cystic Fibrosis and is considered a common pathogenic mutation (see e.g. McKone 2003, Sosnay 2013). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and all classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Mar 04, 2019)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: unknown
Allele origin:
germline
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Johns Hopkins Genomics, Johns Hopkins University
Accession: SCV000992330.1
First in ClinVar: Sep 16, 2019 Last updated: Sep 16, 2019 |
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Pathogenic
(Jun 10, 2020)
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criteria provided, single submitter
Method: clinical testing
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Not provided
Affected status: unknown
Allele origin:
germline
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV001713429.1
First in ClinVar: Jun 15, 2021 Last updated: Jun 15, 2021 |
Number of individuals with the variant: 1
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Pathogenic
(Feb 07, 2020)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: unknown
Allele origin:
germline
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Genome Diagnostics Laboratory, The Hospital for Sick Children
Accession: SCV002507347.1
First in ClinVar: May 16, 2022 Last updated: May 16, 2022 |
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Pathogenic
(Sep 23, 2022)
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criteria provided, single submitter
Method: clinical testing
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CFTR-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004113268.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
Comment:
The CFTR c.1679G>C variant is predicted to result in the amino acid substitution p.Arg560Thr. This variant has been reported in numerous individuals with cystic fibrosis … (more)
The CFTR c.1679G>C variant is predicted to result in the amino acid substitution p.Arg560Thr. This variant has been reported in numerous individuals with cystic fibrosis (Kerem et al. 1990. PubMed ID: 2236053; Castellani et al. 2008. PubMed ID: 18456578). This variant is reported in 0.0053% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/7-117227887-G-C). This variant is interpreted as pathogenic. (less)
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Pathogenic
(Jan 11, 2024)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000074427.11
First in ClinVar: Jul 03, 2013 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 560 of the CFTR protein (p.Arg560Thr). … (more)
This sequence change replaces arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 560 of the CFTR protein (p.Arg560Thr). This variant is present in population databases (rs80055610, gnomAD 0.005%). This missense change has been observed in individual(s) with cystic fibrosis (PMID: 15371902, 23974870). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 7113). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects CFTR function (PMID: 23974870). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(May 06, 2021)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002714483.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.1679G>C pathogenic mutation (also known as p.R560T), located in coding exon 12 of the CFTR gene, results from a G to C substitution at … (more)
The c.1679G>C pathogenic mutation (also known as p.R560T), located in coding exon 12 of the CFTR gene, results from a G to C substitution at nucleotide position 1679. The amino acid change results in arginine to threonine at codon 560, an amino acid with similar properties. However, this change occurs in the last base pair of coding exon 12, which makes it likely to have some effect on normal mRNA splicing. This pathogenic mutation was first reported in a cohort of individuals with cystic fibrosis (Kerem BS et al. Proc. Natl. Acad. Sci. U.S.A., 1990 Nov;87:8447-51). Functional in vitro studies found that cells carrying this pathogenic mutation had no to very little chloride conduction; in addition, this pathogenic mutation is associated with high sweat chloride levels and pancreatic insufficiency Sosnay PR et al. Nat. Genet., 2013 Oct;45:1160-7; Van Goor F et al. J. Cyst. Fibros., 2014 Jan;13:29-36). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(Feb 11, 2015)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
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Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Accession: SCV000281159.1
First in ClinVar: Jun 08, 2016 Last updated: Jun 08, 2016 |
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Congenital bilateral aplasia of vas deferens from CFTR mutation
Cystic fibrosis
Affected status: unknown
Allele origin:
germline
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Baylor Genetics
Accession: SCV001163138.1
First in ClinVar: Mar 01, 2020 Last updated: Mar 01, 2020 |
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Pathogenic
(Dec 04, 2019)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV001193945.2
First in ClinVar: Apr 06, 2020 Last updated: Jul 06, 2020 |
Comment:
NM_000492.3(CFTR):c.1679G>C(R560T) is classified as pathogenic in the context of cystic fibrosis and is associated with the classic form of disease. Sources cited for classification include … (more)
NM_000492.3(CFTR):c.1679G>C(R560T) is classified as pathogenic in the context of cystic fibrosis and is associated with the classic form of disease. Sources cited for classification include the following: PMID 23974870. Classification of NM_000492.3(CFTR):c.1679G>C(R560T) is based on the following criteria: This is a well-established pathogenic variant in the literature that has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.‚Äã (less)
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Pathogenic
(Aug 28, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001470740.1
First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021 |
Comment:
The CFTR c.1679G>C; p.Arg560Thr variant (rs80055610) is known to cause cystic fibrosis (CF) when combined with another CF-causing variant and is associated with pancreatic insufficiency … (more)
The CFTR c.1679G>C; p.Arg560Thr variant (rs80055610) is known to cause cystic fibrosis (CF) when combined with another CF-causing variant and is associated with pancreatic insufficiency (CFTR2 database, SickKids CFTR database, Watson 2004). This variant has been reported as pathogenic by several laboratories in ClinVar (Variation ID: 7113) and is observed on only six chromosomes (6/250518 alleles) in the Genome Aggregation Database. Functional analyses of this variant demonstrate mRNA splicing defects and a marked reduction in translation of mature CFTR protein (Kerem 1990, van Goor 2014). Based on available information, this variant is considered pathogenic. References: CFTR2 database: https://cftr2.org/mutation/general/R560T/ SickKids CFTR database: http://www.genet.sickkids.on.ca/cftr/MutationDetailPage.external?sp=280 Kerem B et al. Identification of mutations in regions corresponding to the two putative nucleotide (ATP)-binding folds of the cystic fibrosis gene. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8447-51. van Goor F et al. Effect of ivacaftor on CFTR forms with missense mutations associated with defects in protein processing or function. J Cyst Fibros. 2014 Jan;13(1):29-36. Watson M et al. Cystic fibrosis population carrier screening: 2004 revision of American College of Medical Genetics mutation panel. Genet Med. 2004 Sep-Oct;6(5):387-91. (less)
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Pathogenic
(Oct 25, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hereditary pancreatitis
Bronchiectasis with or without elevated sweat chloride 1 Cystic fibrosis Congenital bilateral aplasia of vas deferens from CFTR mutation
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002810401.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Oct 28, 2023)
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criteria provided, single submitter
Method: clinical testing
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Bronchiectasis with or without elevated sweat chloride 1
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004213262.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Nov 01, 1990)
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no assertion criteria provided
Method: literature only
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CYSTIC FIBROSIS
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000027734.3
First in ClinVar: Apr 04, 2013 Last updated: Oct 11, 2015 |
Comment on evidence:
In a patient with cystic fibrosis (CF; 219700), Kerem et al. (1990) found a G-to-C change at nucleotide 1811 in exon 11 of the CFTR … (more)
In a patient with cystic fibrosis (CF; 219700), Kerem et al. (1990) found a G-to-C change at nucleotide 1811 in exon 11 of the CFTR gene responsible for substitution of threonine for arginine at amino acid 560 (R560T). (less)
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001740188.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
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Pathogenic
(Feb 07, 2020)
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no assertion criteria provided
Method: clinical testing
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CFTR-related disorders
Affected status: unknown
Allele origin:
germline
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Genome Diagnostics Laboratory, The Hospital for Sick Children
Accession: SCV002507431.1
First in ClinVar: May 16, 2022 Last updated: May 16, 2022 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001968669.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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Pathogenic
(Mar 17, 2017)
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no assertion criteria provided
Method: clinical testing
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CFTR-related disorders
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002080644.1
First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022 |
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not provided
(-)
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no classification provided
Method: literature only
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Cystic fibrosis
Affected status: unknown
Allele origin:
unknown
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GeneReviews
Accession: SCV001622791.2
First in ClinVar: May 23, 2021 Last updated: Oct 01, 2022 |
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Germline Functional Evidence
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 germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Effect of ivacaftor on CFTR forms with missense mutations associated with defects in protein processing or function. | Van Goor F | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society | 2014 | PMID: 23891399 |
Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. | Sosnay PR | Nature genetics | 2013 | PMID: 23974870 |
Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice. | Castellani C | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society | 2008 | PMID: 18456578 |
CFTR mutation distribution among U.S. Hispanic and African American individuals: evaluation in cystic fibrosis patient and carrier screening populations. | Sugarman EA | Genetics in medicine : official journal of the American College of Medical Genetics | 2004 | PMID: 15371903 |
Cystic fibrosis population carrier screening: 2004 revision of American College of Medical Genetics mutation panel. | Watson MS | Genetics in medicine : official journal of the American College of Medical Genetics | 2004 | PMID: 15371902 |
Effect of genotype on phenotype and mortality in cystic fibrosis: a retrospective cohort study. | McKone EF | Lancet (London, England) | 2003 | PMID: 12767731 |
European Epidemiologic Registry of Cystic Fibrosis (ERCF): comparison of major disease manifestations between patients with different classes of mutations. | Koch C | Pediatric pulmonology | 2001 | PMID: 11180668 |
A mutation in CFTR produces different phenotypes depending on chromosomal background. | Kiesewetter S | Nature genetics | 1993 | PMID: 7506096 |
Identification of mutations in regions corresponding to the two putative nucleotide (ATP)-binding folds of the cystic fibrosis gene. | Kerem BS | Proceedings of the National Academy of Sciences of the United States of America | 1990 | PMID: 2236053 |
https://cftr2.org | - | - | - | - |
https://cftr2.org/ | - | - | - | - |
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Text-mined citations for rs80055610 ...
HelpRecord last updated May 27, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.