ClinVar Genomic variation as it relates to human health
NM_000492.4(CFTR):c.3844T>C (p.Trp1282Arg)
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.3844T>C (p.Trp1282Arg)
Variation ID: 53820 Accession: VCV000053820.10
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7q31.2 7: 117642564 (GRCh38) [ NCBI UCSC ] 7: 117282618 (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 Jan 25, 2018 May 1, 2024 Sep 29, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000492.4:c.3844T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000483.3:p.Trp1282Arg missense NC_000007.14:g.117642564T>C NC_000007.13:g.117282618T>C NG_016465.4:g.181781T>C LRG_663:g.181781T>C LRG_663t1:c.3844T>C LRG_663p1:p.Trp1282Arg P13569:p.Trp1282Arg - Protein change
- W1282R
- Other names
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- Canonical SPDI
- NC_000007.14:117642563:T: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.
The Genome Aggregation Database (gnomAD) 0.00001
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
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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 |
3821 | 5195 |
Conditions - Germline
Condition
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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 (4) |
criteria provided, multiple submitters, no conflicts
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Sep 29, 2023 | RCV000577632.10 | |
Pathogenic (1) |
criteria provided, single submitter
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Jul 12, 2023 | RCV003474591.1 |
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
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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
(Jul 12, 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: SCV004213465.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Sep 05, 2022)
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criteria provided, single submitter
Method: curation
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Cystic fibrosis
Affected status: yes
Allele origin:
unknown
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV002574040.1
First in ClinVar: Sep 24, 2022 Last updated: Sep 24, 2022 |
Comment:
This variant was identified in 1 patient with a clinically confirmed diagnosis of cystic fibrosis. The variant was classified in the context of a project … (more)
This variant was identified in 1 patient 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: PM3_VSTR, PM5_STR, PP3, PP4 (less)
Number of individuals with the variant: 1
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Pathogenic
(Sep 29, 2023)
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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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002231222.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
ClinVar contains an entry for this variant (Variation ID: 53820). This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is … (more)
ClinVar contains an entry for this variant (Variation ID: 53820). This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 1282 of the CFTR protein (p.Trp1282Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with cystic fibrosis (PMID: 29504914, 30548586; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CFTR protein function. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Feb 25, 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: SCV002621683.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.W1282R pathogenic mutation (also known as c.3844T>C), located in coding exon 23 of the CFTR gene, results from a T to C substitution at … (more)
The p.W1282R pathogenic mutation (also known as c.3844T>C), located in coding exon 23 of the CFTR gene, results from a T to C substitution at nucleotide position 3844. The tryptophan at codon 1282 is replaced by arginine, an amino acid with dissimilar properties. This mutation was originally reported in an individual with cystic fibrosis; however, the presence of second CFTR variant was unknown (Ivaschenko TE et al. Hum Genet, 1993 Mar;91:63-5). The mutation has also been reported in multiple individuals with cystic fibrosis who had a pathogenic variant on the other chromosome (Ivanov M et al. BMC Med Genomics, 2018 02;11:13; Petrova NV et al. Clin Genet, 2019 03;95:444-447; Petrova NV et al. Genes (Basel), 2020 05;11(5):554; Petrova NV et al. Genes (Basel), 2020 9;11(10):1137). The variant also had minimal CFTR function in FRT cells (Phuan PW et al. Sci Rep, 2019 11;9:17640). Based on internal structural analysis, this variant is anticipated to result in a decrease in structural stability (Liu F et al. Cell, 2017 03;169:85-95.e8). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
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not provided
(-)
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no classification provided
Method: literature only
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CFTR-related disorders
Affected status: yes
Allele origin:
germline
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ClinVar Staff, National Center for Biotechnology Information (NCBI)
Accession: SCV000679092.1
First in ClinVar: Jan 25, 2018 Last updated: Jan 25, 2018 |
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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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Clinical Presentation of the c.3844T>C (p.Trp1282Arg, W1282R) Variant in Russian Cystic Fibrosis Patients. | Petrova NV | Genes | 2020 | PMID: 32992607 |
Analysis of CFTR Mutation Spectrum in Ethnic Russian Cystic Fibrosis Patients. | Petrova NV | Genes | 2020 | PMID: 32429104 |
Nanomolar-potency 'co-potentiator' therapy for cystic fibrosis caused by a defined subset of minimal function CFTR mutants. | Phuan PW | Scientific reports | 2019 | PMID: 31776420 |
Comprehensive genotyping reveals novel CFTR variants in cystic fibrosis patients from the Russian Federation. | Petrova NV | Clinical genetics | 2019 | PMID: 30548586 |
Targeted sequencing reveals complex, phenotype-correlated genotypes in cystic fibrosis. | Ivanov M | BMC medical genomics | 2018 | PMID: 29504914 |
Molecular Structure of the Human CFTR Ion Channel. | Liu F | Cell | 2017 | PMID: 28340353 |
Two new mutations detected by single-strand conformation polymorphism analysis in cystic fibrosis from Russia. | Ivaschenko TE | Human genetics | 1993 | PMID: 7681034 |
Text-mined citations for rs397508616 ...
HelpRecord last updated Sep 29, 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.