The 1393-1G>A variant in CFTR causes cystic fibrosis when combined with another CF-causing variant. It has been previously identified in 2 homozygous and 3 comp ound heterozygous individuals with cystic fibrosis and was found to segregate wi th disease in 1 family member (Dork 1993, Ramalho 2003, Wahab 2004, Ashavaid 200 5, Nikolic 2013). It has not been identified in large population studies. This v ariant occurs in the invariant region (+/- 1,2) of the splice consensus sequence and is predicted to cause altered splicing leading to an abnormal or absent pro tein (Ramalho 2003). In summary, this variant meets our criteria to be classifie d as pathogenic (http://pcpgm.partners.org/LMM) based upon segregation studies, absence from controls, and functional evidence.
ClinVar Genomic variation as it relates to human health
NM_000492.4(CFTR):c.1393-1G>A
Germline
Top reviewed classifications are shown here.
Submission summary:
Reviewed by expert panel
Pathogenic
Mar 2017 by
CFTR2
for
Cystic fibrosis
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000492.4(CFTR):c.1393-1G>A
Variation ID: 53242 Accession: VCV000053242.44
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 7q31.2 7: 117559463 (GRCh38) [ NCBI UCSC ] 7: 117199517 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Sep 30, 2017 Oct 8, 2024 Mar 17, 2017 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000492.4:c.1393-1G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice acceptor NC_000007.14:g.117559463G>A NC_000007.13:g.117199517G>A NG_016465.4:g.98680G>A LRG_663:g.98680G>A LRG_663t1:c.1393-1G>A - Protein change
- -
- Other names
-
1525-1G->A
- Canonical SPDI
- NC_000007.14:117559462:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
The Genome Aggregation Database (gnomAD) 0.00000
Trans-Omics for Precision Medicine (TOPMed) 0.00000
The Genome Aggregation Database (gnomAD), exomes 0.00003
Exome Aggregation Consortium (ExAC) 0.00005
- Links
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 | ||
|---|---|---|---|---|---|---|
| HI score
Help
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. |
|||
| CFTR | - | - |
GRCh38 GRCh37 |
3832 | 5210 | |
| CFTR-AS1 | - | - | - | GRCh38 | - | 512 |
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. |
|---|---|---|---|---|
| Pathogenic (8) |
reviewed by expert panel
|
Mar 17, 2017 | RCV000056347.22 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Mar 15, 2017 | RCV000506518.8 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Apr 8, 2017 | RCV000506225.2 | |
| Pathogenic (1) |
criteria provided, single submitter
|
- | RCV001004449.1 | |
| Pathogenic (2) |
no assertion criteria provided
|
Dec 30, 2023 | RCV001831726.3 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Dec 24, 2023 | RCV003473452.2 |
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. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Mar 17, 2017)
|
reviewed by expert panel
Method: research
|
Cystic fibrosis
Affected status: yes
Allele origin:
germline
|
CFTR2
Study: CFTR2
Accession: SCV000071451.4 First in ClinVar: Oct 18, 2013 Last updated: Jan 06, 2018 |
|
|
|
Pathogenic
(Oct 18, 2013)
|
criteria provided, single submitter
Method: clinical testing
|
Cystic fibrosis
(Autosomal recessive inheritance)
Affected status: not provided
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000205857.4
First in ClinVar: Feb 02, 2015 Last updated: Jan 06, 2018 |
Comment:
The 1393-1G>A variant in CFTR causes cystic fibrosis when combined with another CF-causing variant. It has been previously identified in 2 homozygous and 3 comp … (more)
The 1393-1G>A variant in CFTR causes cystic fibrosis when combined with another CF-causing variant. It has been previously identified in 2 homozygous and 3 comp ound heterozygous individuals with cystic fibrosis and was found to segregate wi th disease in 1 family member (Dork 1993, Ramalho 2003, Wahab 2004, Ashavaid 200 5, Nikolic 2013). It has not been identified in large population studies. This v ariant occurs in the invariant region (+/- 1,2) of the splice consensus sequence and is predicted to cause altered splicing leading to an abnormal or absent pro tein (Ramalho 2003). In summary, this variant meets our criteria to be classifie d as pathogenic (http://pcpgm.partners.org/LMM) based upon segregation studies, absence from controls, and functional evidence. (less)
Number of individuals with the variant: 1
|
|
|
Pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
|
Congenital bilateral aplasia of vas deferens from CFTR mutation
Cystic fibrosis
Affected status: unknown
Allele origin:
germline
|
Baylor Genetics
Accession: SCV001163494.1
First in ClinVar: Mar 01, 2020 Last updated: Mar 01, 2020 |
|
|
|
Pathogenic
(Aug 17, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Cystic fibrosis
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002696017.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.1393-1G>A intronic pathogenic mutation (also known as 1525-1G>A) results from a G to A substitution one nucleotide upstream from coding exon 11 of the … (more)
The c.1393-1G>A intronic pathogenic mutation (also known as 1525-1G>A) results from a G to A substitution one nucleotide upstream from coding exon 11 of the CFTR gene. This mutation was first reported in an Afghani individual with elevated sweat chloride levels and clinical features of cystic fibrosis (CF); however, a second CFTR alteration was not identified (Dörk T et al. Genomics, 1993 Mar;15:688-91). A Serbian individual homozygous for this mutation presented with liver steatosis at age 7 years and later developed respiratory symptoms; he had mild pancreatic insufficiency and elevated sweat chloride levels (Nikolic A et al. J. Cyst. Fibros., 2014 Jan;13:111-3). Splicing analysis in colonic biopsies from two related Pakistani individuals with CF with c.1393-1G>A and p.F508del demonstrated exon skipping or the use of alternative splice sites due to the intronic alteration. Furthermore, the same study demonstrated that CFTR mediated chloride secretion was absent in the colonic biopsies of the affected individuals (Ramalho AS et al. J. Med. Genet., 2003 Jul;40:e88). In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation. (less)
|
|
|
Pathogenic
(Dec 24, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Bronchiectasis with or without elevated sweat chloride 1
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004213368.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
|
|
|
Pathogenic
(Mar 15, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000603063.1
First in ClinVar: Sep 30, 2017 Last updated: Sep 30, 2017 |
|
|
|
Pathogenic
(Mar 30, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Cystic fibrosis
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000696839.1
First in ClinVar: Jan 06, 2018 Last updated: Jan 06, 2018 |
Comment:
Variant summary: The c.1393-1G>A in CFTR gene is a splice-site variant that alters a highly conserved nucleotide. 5/5 in silico tools via Alamut predict this … (more)
Variant summary: The c.1393-1G>A in CFTR gene is a splice-site variant that alters a highly conserved nucleotide. 5/5 in silico tools via Alamut predict this variant to disrupt a canonical splicing acceptor sequence, although these predictions are yet to be confirmed by the functional studies. The variant is present in control dataset of ExAC at a low frequency of 0.000049 (6/121108 chrs tested) which does not exceed the estimated maximum allele frequency for a pathogenic allele in this gene (0.0129). This variant appears to be very common in Palestina (Siryani, 2015). The variant was found homozygously or in compound heterozygosity in multiple affected individuals with established dx of CF. Patients, homozygous for the variant of interest, presented with elevated sweat Cl- (ranging from 110 to 148 mmol/L) and PI. Lastly, multiple reputable databases/diagnostic centers classified the variant of interest as Pathogenic. Taken together, the variant was classified as Pathogenic. (less)
|
|
|
Pathogenic
(Jan 29, 2018)
|
criteria provided, single submitter
Method: curation
|
cystic fibrosis
Affected status: yes
Allele origin:
germline
|
CFTR-France
Accession: SCV001169562.1
First in ClinVar: Mar 16, 2020 Last updated: Mar 16, 2020 |
|
|
|
Pathogenic
(Apr 08, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000601043.2
First in ClinVar: Sep 30, 2017 Last updated: Jan 01, 2022 |
|
|
|
Pathogenic
(Feb 01, 2013)
|
criteria provided, single submitter
Method: clinical testing
|
Cystic fibrosis
Affected status: yes
Allele origin:
germline
|
Arcensus
Accession: SCV002564583.1
First in ClinVar: Dec 17, 2022 Last updated: Dec 17, 2022 |
|
|
|
Pathogenic
(Jan 05, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Cystic fibrosis
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001579489.4
First in ClinVar: May 10, 2021 Last updated: Feb 20, 2024 |
Comment:
This sequence change affects an acceptor splice site in intron 10 of the CFTR gene. It is expected to disrupt RNA splicing. Variants that disrupt … (more)
This sequence change affects an acceptor splice site in intron 10 of the CFTR gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922). This variant is present in population databases (rs397508200, gnomAD 0.03%). Disruption of this splice site has been observed in individual(s) with cystic fibrosis and congenital bilateral absence of the vas deferens (PMID: 7682196, 9239681, 9482579, 15727251, 17662673, 18373402, 18782298, 21198395, 21909392, 23933162, 25688174, 26208274, 26708955). This variant is also known as c.1525-1G>A. ClinVar contains an entry for this variant (Variation ID: 53242). 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)
|
|
|
Pathogenic
(Mar 17, 2017)
|
no assertion criteria provided
Method: clinical testing
|
CFTR-related disorders
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV002080586.1
First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022 |
|
|
|
Pathogenic
(Dec 30, 2023)
|
no assertion criteria provided
Method: clinical testing
|
CFTR-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004718913.2
First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024 |
Comment:
The CFTR c.1393-1G>A variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. This variant, previously described as c.1525-1G>A using … (more)
The CFTR c.1393-1G>A variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. This variant, previously described as c.1525-1G>A using legacy nomenclature, has been reported to be causative for cystic fibrosis (Castellani et al. 2008. PubMed ID: 18456578; Supplemental table 2, Sosnay et al. 2013. PubMed ID: 23974870). The c.1393-1G>A variant has also been reported in patient with idiopathic chronic pancreatitis who had a corresponding pathogenic variant in the SPINK1 gene (Supplemental table 1, Midha et al. 2010. PubMed ID: 20551465). This variant is reported in 0.026% of alleles in individuals of South Asian descent in gnomAD. Variants that disrupt the consensus splice acceptor site in CFTR are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
Cystic fibrosis
Affected status: yes
Allele origin:
germline
|
Dr.Nikuei Genetic Center
Accession: SCV005061397.1
First in ClinVar: Jun 23, 2024 Last updated: Jun 23, 2024 |
|
|
| click to load more click to collapse | |||||
Comment:
Comment:
The c.1393-1G>A intronic pathogenic mutation (also known as 1525-1G>A) results from a G to A substitution one nucleotide upstream from coding exon 11 of the CFTR gene. This mutation was first reported in an Afghani individual with elevated sweat chloride levels and clinical features of cystic fibrosis (CF); however, a second CFTR alteration was not identified (Dörk T et al. Genomics, 1993 Mar;15:688-91). A Serbian individual homozygous for this mutation presented with liver steatosis at age 7 years and later developed respiratory symptoms; he had mild pancreatic insufficiency and elevated sweat chloride levels (Nikolic A et al. J. Cyst. Fibros., 2014 Jan;13:111-3). Splicing analysis in colonic biopsies from two related Pakistani individuals with CF with c.1393-1G>A and p.F508del demonstrated exon skipping or the use of alternative splice sites due to the intronic alteration. Furthermore, the same study demonstrated that CFTR mediated chloride secretion was absent in the colonic biopsies of the affected individuals (Ramalho AS et al. J. Med. Genet., 2003 Jul;40:e88). In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation.
Comment:
Variant summary: The c.1393-1G>A in CFTR gene is a splice-site variant that alters a highly conserved nucleotide. 5/5 in silico tools via Alamut predict this variant to disrupt a canonical splicing acceptor sequence, although these predictions are yet to be confirmed by the functional studies. The variant is present in control dataset of ExAC at a low frequency of 0.000049 (6/121108 chrs tested) which does not exceed the estimated maximum allele frequency for a pathogenic allele in this gene (0.0129). This variant appears to be very common in Palestina (Siryani, 2015). The variant was found homozygously or in compound heterozygosity in multiple affected individuals with established dx of CF. Patients, homozygous for the variant of interest, presented with elevated sweat Cl- (ranging from 110 to 148 mmol/L) and PI. Lastly, multiple reputable databases/diagnostic centers classified the variant of interest as Pathogenic. Taken together, the variant was classified as Pathogenic.
Comment:
This sequence change affects an acceptor splice site in intron 10 of the CFTR gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922). This variant is present in population databases (rs397508200, gnomAD 0.03%). Disruption of this splice site has been observed in individual(s) with cystic fibrosis and congenital bilateral absence of the vas deferens (PMID: 7682196, 9239681, 9482579, 15727251, 17662673, 18373402, 18782298, 21198395, 21909392, 23933162, 25688174, 26208274, 26708955). This variant is also known as c.1525-1G>A. ClinVar contains an entry for this variant (Variation ID: 53242). 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.
Comment:
The CFTR c.1393-1G>A variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. This variant, previously described as c.1525-1G>A using legacy nomenclature, has been reported to be causative for cystic fibrosis (Castellani et al. 2008. PubMed ID: 18456578; Supplemental table 2, Sosnay et al. 2013. PubMed ID: 23974870). The c.1393-1G>A variant has also been reported in patient with idiopathic chronic pancreatitis who had a corresponding pathogenic variant in the SPINK1 gene (Supplemental table 1, Midha et al. 2010. PubMed ID: 20551465). This variant is reported in 0.026% of alleles in individuals of South Asian descent in gnomAD. Variants that disrupt the consensus splice acceptor site in CFTR are expected to be pathogenic. This variant is interpreted as pathogenic.
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. |
Comment:
The 1393-1G>A variant in CFTR causes cystic fibrosis when combined with another CF-causing variant. It has been previously identified in 2 homozygous and 3 comp ound heterozygous individuals with cystic fibrosis and was found to segregate wi th disease in 1 family member (Dork 1993, Ramalho 2003, Wahab 2004, Ashavaid 200 5, Nikolic 2013). It has not been identified in large population studies. This v ariant occurs in the invariant region (+/- 1,2) of the splice consensus sequence and is predicted to cause altered splicing leading to an abnormal or absent pro tein (Ramalho 2003). In summary, this variant meets our criteria to be classifie d as pathogenic (http://pcpgm.partners.org/LMM) based upon segregation studies, absence from controls, and functional evidence.
Comment:
The c.1393-1G>A intronic pathogenic mutation (also known as 1525-1G>A) results from a G to A substitution one nucleotide upstream from coding exon 11 of the CFTR gene. This mutation was first reported in an Afghani individual with elevated sweat chloride levels and clinical features of cystic fibrosis (CF); however, a second CFTR alteration was not identified (Dörk T et al. Genomics, 1993 Mar;15:688-91). A Serbian individual homozygous for this mutation presented with liver steatosis at age 7 years and later developed respiratory symptoms; he had mild pancreatic insufficiency and elevated sweat chloride levels (Nikolic A et al. J. Cyst. Fibros., 2014 Jan;13:111-3). Splicing analysis in colonic biopsies from two related Pakistani individuals with CF with c.1393-1G>A and p.F508del demonstrated exon skipping or the use of alternative splice sites due to the intronic alteration. Furthermore, the same study demonstrated that CFTR mediated chloride secretion was absent in the colonic biopsies of the affected individuals (Ramalho AS et al. J. Med. Genet., 2003 Jul;40:e88). In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation.
Comment:
Variant summary: The c.1393-1G>A in CFTR gene is a splice-site variant that alters a highly conserved nucleotide. 5/5 in silico tools via Alamut predict this variant to disrupt a canonical splicing acceptor sequence, although these predictions are yet to be confirmed by the functional studies. The variant is present in control dataset of ExAC at a low frequency of 0.000049 (6/121108 chrs tested) which does not exceed the estimated maximum allele frequency for a pathogenic allele in this gene (0.0129). This variant appears to be very common in Palestina (Siryani, 2015). The variant was found homozygously or in compound heterozygosity in multiple affected individuals with established dx of CF. Patients, homozygous for the variant of interest, presented with elevated sweat Cl- (ranging from 110 to 148 mmol/L) and PI. Lastly, multiple reputable databases/diagnostic centers classified the variant of interest as Pathogenic. Taken together, the variant was classified as Pathogenic.
Comment:
This sequence change affects an acceptor splice site in intron 10 of the CFTR gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922). This variant is present in population databases (rs397508200, gnomAD 0.03%). Disruption of this splice site has been observed in individual(s) with cystic fibrosis and congenital bilateral absence of the vas deferens (PMID: 7682196, 9239681, 9482579, 15727251, 17662673, 18373402, 18782298, 21198395, 21909392, 23933162, 25688174, 26208274, 26708955). This variant is also known as c.1525-1G>A. ClinVar contains an entry for this variant (Variation ID: 53242). 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.
Comment:
The CFTR c.1393-1G>A variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. This variant, previously described as c.1525-1G>A using legacy nomenclature, has been reported to be causative for cystic fibrosis (Castellani et al. 2008. PubMed ID: 18456578; Supplemental table 2, Sosnay et al. 2013. PubMed ID: 23974870). The c.1393-1G>A variant has also been reported in patient with idiopathic chronic pancreatitis who had a corresponding pathogenic variant in the SPINK1 gene (Supplemental table 1, Midha et al. 2010. PubMed ID: 20551465). This variant is reported in 0.026% of alleles in individuals of South Asian descent in gnomAD. Variants that disrupt the consensus splice acceptor site in CFTR are expected to be pathogenic. This variant is interpreted as pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Using ClinVar as a Resource to Support Variant Interpretation. | Harrison SM | Current protocols in human genetics | 2016 | PMID: 27037489 |
| The Spectrum of CFTR Variants in Nonwhite Cystic Fibrosis Patients: Implications for Molecular Diagnostic Testing. | Schrijver I | The Journal of molecular diagnostics : JMD | 2016 | PMID: 26708955 |
| Distribution of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutations in a Cohort of Patients Residing in Palestine. | Siryani I | PloS one | 2015 | PMID: 26208274 |
| Next generation sequencing to determine the cystic fibrosis mutation spectrum in Palestinian population. | Essawi O | Disease markers | 2015 | PMID: 25688174 |
| RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. | Xiong HY | Science (New York, N.Y.) | 2015 | PMID: 25525159 |
| Clinical presentation of mild cystic fibrosis in a Serbian patient homozygous for the CFTR mutation c.1393-1G>A. | Nikolic A | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society | 2014 | PMID: 23933162 |
| Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. | Sosnay PR | Nature genetics | 2013 | PMID: 23974870 |
| The K+ channel opener 1-EBIO potentiates residual function of mutant CFTR in rectal biopsies from cystic fibrosis patients. | Roth EK | PloS one | 2011 | PMID: 21909392 |
| Spectrum of CFTR gene mutations in Iranian Azeri Turkish patients with cystic fibrosis. | Bonyadi M | Genetic testing and molecular biomarkers | 2011 | PMID: 21198395 |
| Idiopathic chronic pancreatitis in India: phenotypic characterisation and strong genetic susceptibility due to SPINK1 and CFTR gene mutations. | Midha S | Gut | 2010 | PMID: 20551465 |
| Identification and characterization of CFTR gene mutations in Indian CF patients. | Sharma N | Annals of human genetics | 2009 | PMID: 18782298 |
| CFTR mutations in Turkish and North African cystic fibrosis patients in Europe: implications for screening. | Lakeman P | Genetic testing | 2008 | PMID: 18373402 |
| Analysis of the CFTR gene in Iranian cystic fibrosis patients: identification of eight novel mutations. | Alibakhshi R | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society | 2008 | PMID: 17662673 |
| A haplotype framework for cystic fibrosis mutations in Iran. | Elahi E | The Journal of molecular diagnostics : JMD | 2006 | PMID: 16436643 |
| Splicing in action: assessing disease causing sequence changes. | Baralle D | Journal of medical genetics | 2005 | PMID: 16199547 |
| Application of multiplex ARMS and SSCP/HD analysis in molecular diagnosis of cystic fibrosis in Indian patients. | Ashavaid TF | Molecular diagnosis : a journal devoted to the understanding of human disease through the clinical application of molecular biology | 2005 | PMID: 16137181 |
| Spectrum of cystic fibrosis mutations in Serbia and Montenegro and strategy for prenatal diagnosis. | Radivojevic D | Genetic testing | 2004 | PMID: 15727251 |
| Rare CFTR mutation 1525-1G>A in a Pakistani patient. | Wahab A | Journal of tropical pediatrics | 2004 | PMID: 15088804 |
| Transcript analysis of the cystic fibrosis splicing mutation 1525-1G>A shows use of multiple alternative splicing sites and suggests a putative role of exonic splicing enhancers. | Ramalho AS | Journal of medical genetics | 2003 | PMID: 12843337 |
| Cystic fibrosis: a worldwide analysis of CFTR mutations--correlation with incidence data and application to screening. | Bobadilla JL | Human mutation | 2002 | PMID: 12007216 |
| Relation between mutations of the cystic fibrosis gene and idiopathic pancreatitis. | Cohn JA | The New England journal of medicine | 1998 | PMID: 9725922 |
| Detection of five novel mutations of the cystic fibrosis transmembrane regulator (CFTR) gene in Pakistani patients with cystic fibrosis: Y569D, Q98X, 296+12(T>C), 1161delC and 621+2(T>C). | Malone G | Human mutation | 1998 | PMID: 9482579 |
| Characterization of more than 85% of cystic fibrosis alleles in the Greek population, including five novel mutations. | Tzetis M | Human genetics | 1997 | PMID: 9003508 |
| Mutations in the cystic fibrosis gene in men with congenital bilateral absence of the vas deferens. | De Braekeleer M | Molecular human reproduction | 1996 | PMID: 9239681 |
| CFTR gene variant for patients with congenital absence of vas deferens. | Zielenski J | American journal of human genetics | 1995 | PMID: 7573058 |
| Molecular basis of defective anion transport in L cells expressing recombinant forms of CFTR. | Yang Y | Human molecular genetics | 1993 | PMID: 7691345 |
| Four novel cystic fibrosis mutations in splice junction sequences affecting the CFTR nucleotide binding folds. | Dörk T | Genomics | 1993 | PMID: 7682196 |
| A cluster of cystic fibrosis mutations in the first nucleotide-binding fold of the cystic fibrosis conductance regulator protein. | Cutting GR | Nature | 1990 | PMID: 1695717 |
| https://cftr2.org | - | - | - | - |
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Text-mined citations for rs397508200 ...
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Record last updated Nov 25, 2024
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