Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Common pathogenic variant among individuals of Dutch-German Mennonite background (Bech-Hansen et al., 1998); Not observed at significant frequency in large population cohorts (gnomAD); Also known as L991insC using alternate nomenclature; This variant is associated with the following publications: (PMID: 9662399, 28162000, 10900517, 18348259, 22744390, 33668843, 20301423, 9662400)
ClinVar Genomic variation as it relates to human health
NM_001256789.3(CACNA1F):c.3133dup (p.Leu1045fs)
Germline
Classification
Help
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.
(10)
Help
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.
Pathogenic
10
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001256789.3(CACNA1F):c.3133dup (p.Leu1045fs)
Variation ID: 21443 Accession: VCV000021443.46
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: Xp11.23 X: 49216484-49216485 (GRCh38) [ NCBI UCSC ] X: 49072944-49072945 (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 May 3, 2013 Oct 20, 2024 Sep 30, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001256789.3:c.3133dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001243718.1:p.Leu1045fs frameshift NM_001256790.3:c.2971dup NP_001243719.1:p.Leu991fs frameshift NM_005183.2:c.3166dupC NM_005183.2:c.3167_3168dupC NM_005183.3:c.3166dupC NM_005183.4:c.3166dup NP_005174.2:p.Leu1056fs frameshift NC_000023.11:g.49216488dup NC_000023.10:g.49072948dup NG_009095.2:g.21882dup - Protein change
- L1056fs, L991fs, L1045fs
- Other names
- -
- Canonical SPDI
- NC_000023.11:49216484:GGGG:GGGGG
-
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.
- -
- 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. |
|||
| CACNA1F | - | - |
GRCh38 GRCh37 |
1155 | 1404 | |
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 (4) |
criteria provided, multiple submitters, no conflicts
|
Sep 30, 2024 | RCV000020629.9 | |
| Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
|
Dec 29, 2023 | RCV000790658.39 | |
|
CACNA1F-related disorder
|
Pathogenic (1) |
criteria provided, single submitter
|
May 2, 2023 | RCV003398551.5 |
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
(Jun 08, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Congenital stationary night blindness 2A
Affected status: yes
Allele origin:
germline
|
MGZ Medical Genetics Center
Accession: SCV002580093.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
Comment:
ACMG criteria applied: PVS1, PP1_STR, PS4_MOD, PM3, PM2_SUP
|
Number of individuals with the variant: 1
Sex: male
|
|
|
Pathogenic
(Feb 01, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001790147.3
First in ClinVar: Aug 21, 2021 Last updated: Mar 04, 2023 |
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Common … (more)
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Common pathogenic variant among individuals of Dutch-German Mennonite background (Bech-Hansen et al., 1998); Not observed at significant frequency in large population cohorts (gnomAD); Also known as L991insC using alternate nomenclature; This variant is associated with the following publications: (PMID: 9662399, 28162000, 10900517, 18348259, 22744390, 33668843, 20301423, 9662400) (less)
|
|
|
Pathogenic
(Sep 02, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000334438.3
First in ClinVar: Dec 06, 2016 Last updated: Jul 30, 2019 |
Number of individuals with the variant: 2
Sex: mixed
|
|
|
Pathogenic
(Oct 23, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
(X-linked recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001447326.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Cone monochromatism (present) , Achromatopsia (present) , Congenital stationary night blindness (present)
Sex: male
|
|
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Pathogenic
(May 02, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
CACNA1F-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004121492.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
Comment:
The CACNA1F c.3166dupC variant is predicted to result in a frameshift and premature protein termination (p.Leu1056Profs*11). This variant has been reported in multiple individuals with … (more)
The CACNA1F c.3166dupC variant is predicted to result in a frameshift and premature protein termination (p.Leu1056Profs*11). This variant has been reported in multiple individuals with congenital stationary night blindness (see for example Vincent and Héon et al. 2012. PubMed ID: 22744390; reported as c.3133insC in Strom et al. 1998. PubMed ID: 9662399). Frameshift variants in CACNA1F are expected to be pathogenic and this variant has been classified as pathogenic by multiple independent submitters to the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/21443). Given all the evidence, we interpret c.3166dup (p.Leu1056Profs*11) as pathogenic. (less)
|
|
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Pathogenic
(Dec 29, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001588982.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Leu1056Profs*11) in the CACNA1F gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Leu1056Profs*11) in the CACNA1F gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CACNA1F are known to be pathogenic (PMID: 9662399, 11281458, 17525176, 22194652, 24124559, 26992781). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with X-linked congenital stationary night blindness (PMID: 9662399, 9662400, 10900517). It is commonly reported in individuals of Mennonite ancestry (PMID: 9662399, 9662400, 10900517). This variant is also known as 3133inC, Leu991insC, and Leu1056insC. ClinVar contains an entry for this variant (Variation ID: 21443). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(Sep 30, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Congenital stationary night blindness 2A
(X-linked dominant inheritance)
Affected status: yes
Allele origin:
maternal
|
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV004032251.2
First in ClinVar: Sep 09, 2023 Last updated: Oct 13, 2024 |
Comment:
Criteria applied: PVS1,PS4_MOD,PM2
Clinical Features:
Mild global developmental delay (present) , High myopia (present) , Neonatal seizure (present) , Nystagmus (present) , Astigmatism (present) , Clinodactyly (present) , Ventricular septal … (more)
Mild global developmental delay (present) , High myopia (present) , Neonatal seizure (present) , Nystagmus (present) , Astigmatism (present) , Clinodactyly (present) , Ventricular septal defect (present) , Patent ductus arteriosus (present) , Prominent fingertip pads (present) (less)
Sex: male
|
|
|
Pathogenic
(May 01, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001247593.26
First in ClinVar: May 12, 2020 Last updated: Oct 20, 2024 |
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Jul 01, 1998)
|
no assertion criteria provided
Method: literature only
|
NIGHT BLINDNESS, CONGENITAL STATIONARY, TYPE 2A
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000032616.3
First in ClinVar: Apr 04, 2013 Last updated: Jul 23, 2015 |
Comment on evidence:
In 15 families with congenital stationary night blindness type 2A (CSNB2A; 300071) and the common Mennonite haplotype, suggesting that these families share a founder mutation … (more)
In 15 families with congenital stationary night blindness type 2A (CSNB2A; 300071) and the common Mennonite haplotype, suggesting that these families share a founder mutation (Boycott et al. (1998)), Bech-Hansen et al. (1998) found insertion of a single C nucleotide at codon 991 for leucine (L991insC). The insertion caused a frameshift with stop codon 1001. (less)
|
|
|
pathologic
(Apr 26, 2012)
|
no assertion criteria provided
Method: curation
|
Congenital Stationary Night Blindness, X-Linked
Affected status: not provided
Allele origin:
not provided
|
GeneReviews
Accession: SCV000041144.2
First in ClinVar: Apr 04, 2013 Last updated: May 03, 2013 |
Comment:
Converted during submission to Pathogenic.
|
Comment:
Comment:
The CACNA1F c.3166dupC variant is predicted to result in a frameshift and premature protein termination (p.Leu1056Profs*11). This variant has been reported in multiple individuals with congenital stationary night blindness (see for example Vincent and Héon et al. 2012. PubMed ID: 22744390; reported as c.3133insC in Strom et al. 1998. PubMed ID: 9662399). Frameshift variants in CACNA1F are expected to be pathogenic and this variant has been classified as pathogenic by multiple independent submitters to the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/21443). Given all the evidence, we interpret c.3166dup (p.Leu1056Profs*11) as pathogenic.
Comment:
This sequence change creates a premature translational stop signal (p.Leu1056Profs*11) in the CACNA1F gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CACNA1F are known to be pathogenic (PMID: 9662399, 11281458, 17525176, 22194652, 24124559, 26992781). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with X-linked congenital stationary night blindness (PMID: 9662399, 9662400, 10900517). It is commonly reported in individuals of Mennonite ancestry (PMID: 9662399, 9662400, 10900517). This variant is also known as 3133inC, Leu991insC, and Leu1056insC. ClinVar contains an entry for this variant (Variation ID: 21443). For these reasons, this variant has been classified as Pathogenic.
Comment:
Criteria applied: PVS1,PS4_MOD,PM2
Comment:
Converted during submission to 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:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Common pathogenic variant among individuals of Dutch-German Mennonite background (Bech-Hansen et al., 1998); Not observed at significant frequency in large population cohorts (gnomAD); Also known as L991insC using alternate nomenclature; This variant is associated with the following publications: (PMID: 9662399, 28162000, 10900517, 18348259, 22744390, 33668843, 20301423, 9662400)
Comment:
The CACNA1F c.3166dupC variant is predicted to result in a frameshift and premature protein termination (p.Leu1056Profs*11). This variant has been reported in multiple individuals with congenital stationary night blindness (see for example Vincent and Héon et al. 2012. PubMed ID: 22744390; reported as c.3133insC in Strom et al. 1998. PubMed ID: 9662399). Frameshift variants in CACNA1F are expected to be pathogenic and this variant has been classified as pathogenic by multiple independent submitters to the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/21443). Given all the evidence, we interpret c.3166dup (p.Leu1056Profs*11) as pathogenic.
Comment:
This sequence change creates a premature translational stop signal (p.Leu1056Profs*11) in the CACNA1F gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CACNA1F are known to be pathogenic (PMID: 9662399, 11281458, 17525176, 22194652, 24124559, 26992781). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with X-linked congenital stationary night blindness (PMID: 9662399, 9662400, 10900517). It is commonly reported in individuals of Mennonite ancestry (PMID: 9662399, 9662400, 10900517). This variant is also known as 3133inC, Leu991insC, and Leu1056insC. ClinVar contains an entry for this variant (Variation ID: 21443). For these reasons, this variant has been classified as Pathogenic.
Comment:
Criteria applied: PVS1,PS4_MOD,PM2
Comment:
Converted during submission to Pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| X-Linked Congenital Stationary Night Blindness. | Adam MP | - | 2019 | PMID: 20301423 |
| Molecular genetics of cone-rod dystrophy in Chinese patients: New data from 61 probands and mutation overview of 163 probands. | Huang L | Experimental eye research | 2016 | PMID: 26992781 |
| A novel large in-frame deletion within the CACNA1F gene associates with a cone-rod dystrophy 3-like phenotype. | Hauke J | PloS one | 2013 | PMID: 24124559 |
| A novel p.Gly603Arg mutation in CACNA1F causes Åland island eye disease and incomplete congenital stationary night blindness phenotypes in a family. | Vincent A | Molecular vision | 2011 | PMID: 22194652 |
| A novel CACNA1F gene mutation causes Aland Island eye disease. | Jalkanen R | Investigative ophthalmology & visual science | 2007 | PMID: 17525176 |
| A summary of 20 CACNA1F mutations identified in 36 families with incomplete X-linked congenital stationary night blindness, and characterization of splice variants. | Boycott KM | Human genetics | 2001 | PMID: 11281458 |
| Clinical variability among patients with incomplete X-linked congenital stationary night blindness and a founder mutation in CACNA1F. | Boycott KM | Canadian journal of ophthalmology. Journal canadien d'ophtalmologie | 2000 | PMID: 10900517 |
| Loss-of-function mutations in a calcium-channel alpha1-subunit gene in Xp11.23 cause incomplete X-linked congenital stationary night blindness. | Bech-Hansen NT | Nature genetics | 1998 | PMID: 9662400 |
| An L-type calcium-channel gene mutated in incomplete X-linked congenital stationary night blindness. | Strom TM | Nature genetics | 1998 | PMID: 9662399 |
| Evidence for genetic heterogeneity in X-linked congenital stationary night blindness. | Boycott KM | American journal of human genetics | 1998 | PMID: 9529339 |
Text-mined citations for rs80359870 ...
HelpThese 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 25, 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.