ClinVar Genomic variation as it relates to human health
NM_001079802.2(FKTN):c.642dup (p.Asp215Ter)
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_001079802.2(FKTN):c.642dup (p.Asp215Ter)
Variation ID: 93523 Accession: VCV000093523.28
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 9q31.2 9: 105604483-105604484 (GRCh38) [ NCBI UCSC ] 9: 108366764-108366765 (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 Jun 17, 2024 Mar 29, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001079802.2:c.642dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001073270.1:p.Asp215Ter nonsense NM_001079802.1:c.642dupT NM_001198963.2:c.642dup NP_001185892.1:p.Asp215Ter nonsense NM_001351496.2:c.642dup NP_001338425.1:p.Asp215Ter nonsense NM_001351497.2:c.573dup NP_001338426.1:p.Asp192Ter nonsense NM_001351498.2:c.642dup NP_001338427.1:p.Asp215Ter nonsense NM_001351499.2:c.246dup NP_001338428.1:p.Asp83Ter nonsense NM_001351500.2:c.246dup NP_001338429.1:p.Asp83Ter nonsense NM_001351501.2:c.246dup NP_001338430.1:p.Asp83Ter nonsense NM_001351502.2:c.246dup NP_001338431.1:p.Asp83Ter nonsense NM_006731.2:c.642dup NP_006722.2:p.Asp215Ter nonsense NM_006731.2:c.642dupT NR_147213.2:n.857dup non-coding transcript variant NR_147214.2:n.765dup non-coding transcript variant NC_000009.12:g.105604487dup NC_000009.11:g.108366768dup NG_008754.1:g.51358dup LRG_434:g.51358dup LRG_434t1:c.642dup LRG_434p1:p.Asp215Ter LRG_434t2:c.642dup LRG_434p2:p.Asp215Ter - Protein change
- D192*, D215*, D83*
- Other names
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- Canonical SPDI
- NC_000009.12:105604483:TTTT:TTTTT
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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
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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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FKTN | - | - |
GRCh38 GRCh37 |
998 | 1048 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Jan 16, 2023 | RCV000079438.19 | |
Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Sep 21, 2020 | RCV000169031.3 | |
Pathogenic (2) |
criteria provided, single submitter
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Jan 29, 2024 | RCV000472307.8 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 21, 2021 | RCV002490691.1 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 29, 2024 | RCV003474679.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Dec 9, 2022 | RCV003162509.2 |
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
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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
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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
(Jan 30, 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: SCV000281461.2
First in ClinVar: Jun 09, 2016 Last updated: Aug 29, 2016 |
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Pathogenic
(Sep 21, 2020)
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criteria provided, single submitter
Method: clinical testing
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Fukuyama congenital muscular dystrophy
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001437307.1
First in ClinVar: Oct 08, 2020 Last updated: Oct 08, 2020 |
Comment:
Variant summary: FKTN c.642dupT (p.Asp215X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: FKTN c.642dupT (p.Asp215X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 0.00014 in 250372 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in FKTN causing Walker-Warburg Syndrome (0.00014 vs 0.00046). c.642dupT has been reported in the literature in individuals affected with Walker-Warburg Syndrome (Manzini_2012, Berg_2017). Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Likely pathogenic
(Mar 22, 2014)
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criteria provided, single submitter
Method: literature only
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Fukuyama congenital muscular dystrophy
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000220181.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022 |
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Pathogenic
(Oct 21, 2021)
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criteria provided, single submitter
Method: clinical testing
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Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 Autosomal recessive limb-girdle muscular dystrophy type 2M Dilated cardiomyopathy 1X Muscular dystrophy-dystroglycanopathy (congenital without intellectual disability), type B4
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002809170.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Jan 16, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000491171.4
First in ClinVar: Aug 29, 2016 Last updated: Feb 07, 2023 |
Comment:
Observed in a patient with early-life epilepsy and structural brain malformation; zygosity was not explicitly stated (Berg et al., 2017); Nonsense variant predicted to result … (more)
Observed in a patient with early-life epilepsy and structural brain malformation; zygosity was not explicitly stated (Berg et al., 2017); Nonsense 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; This variant is associated with the following publications: (PMID: 22958903, 23757202, 28759667) (less)
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Likely pathogenic
(Sep 22, 2021)
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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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Revvity Omics, Revvity
Accession: SCV002017782.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Dec 09, 2022)
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criteria provided, single submitter
Method: clinical testing
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Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV003912553.2
First in ClinVar: Apr 15, 2023 Last updated: May 01, 2024 |
Comment:
The c.642dupT pathogenic mutation, located in coding exon 4 of the FKTN gene, results from a duplication of T at nucleotide position 642, causing a … (more)
The c.642dupT pathogenic mutation, located in coding exon 4 of the FKTN gene, results from a duplication of T at nucleotide position 642, causing a translational frameshift with a predicted alternate stop codon (p.D215*). This variant has been detected in the homozygous state in an individual with Walker-Warburg syndrome and was also detected in an individual with early-onset epilepsy and brain malformation for whom zygosity detail was not provided (Manzini MC et al. Am J Hum Genet, 2012 Sep;91:541-7; Berg AT et al. JAMA Pediatr, 2017 Sep;171:863-871). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(Mar 29, 2024)
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criteria provided, single submitter
Method: clinical testing
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Dilated cardiomyopathy 1X
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004199721.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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Pathogenic
(Dec 06, 2012)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000331086.3
First in ClinVar: Dec 06, 2016 Last updated: Jul 31, 2019 |
Number of individuals with the variant: 1
Sex: mixed
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Pathogenic
(Jan 29, 2024)
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criteria provided, single submitter
Method: clinical testing
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Walker-Warburg congenital muscular dystrophy
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000546097.7
First in ClinVar: Apr 17, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Asp215*) in the FKTN gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Asp215*) in the FKTN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FKTN are known to be pathogenic (PMID: 17044012, 17878207, 18752264). This variant is present in population databases (rs766898395, gnomAD 0.1%). This premature translational stop signal has been observed in individual(s) with Walker-Warburg syndrome (PMID: 17878207, 22958903). ClinVar contains an entry for this variant (Variation ID: 93523). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(May 27, 2020)
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no assertion criteria provided
Method: clinical testing
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Walker-Warburg congenital muscular dystrophy
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002079589.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 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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Early-Life Epilepsies and the Emerging Role of Genetic Testing. | Berg AT | JAMA pediatrics | 2017 | PMID: 28759667 |
Exome sequencing and functional validation in zebrafish identify GTDC2 mutations as a cause of Walker-Warburg syndrome. | Manzini MC | American journal of human genetics | 2012 | PMID: 22958903 |
Ethnically diverse causes of Walker-Warburg syndrome (WWS): FCMD mutations are a more common cause of WWS outside of the Middle East. | Manzini MC | Human mutation | 2008 | PMID: 18752264 |
Refining genotype phenotype correlations in muscular dystrophies with defective glycosylation of dystroglycan. | Godfrey C | Brain : a journal of neurology | 2007 | PMID: 17878207 |
Fukutin gene mutations in steroid-responsive limb girdle muscular dystrophy. | Godfrey C | Annals of neurology | 2006 | PMID: 17044012 |
Text-mined citations for rs398123557 ...
HelpRecord last updated Jun 17, 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.