ClinVar Genomic variation as it relates to human health
NM_001079802.2(FKTN):c.1106del (p.Phe369fs)
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.1106del (p.Phe369fs)
Variation ID: 371091 Accession: VCV000371091.15
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 9q31.2 9: 105619989 (GRCh38) [ NCBI UCSC ] 9: 108382270 (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 6, 2017 May 1, 2024 Jan 24, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001079802.2:c.1106del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001073270.1:p.Phe369fs frameshift NM_001079802.1:c.1100delT NM_001079802.1:c.1106delT frameshift NM_001198963.2:c.1106del NP_001185892.1:p.Phe369fs frameshift NM_001351496.2:c.1106del NP_001338425.1:p.Phe369fs frameshift NM_001351497.2:c.1037del NP_001338426.1:p.Phe346fs frameshift NM_001351498.2:c.1106del NP_001338427.1:p.Phe369fs frameshift NM_001351499.2:c.710del NP_001338428.1:p.Phe237fs frameshift NM_001351500.2:c.710del NP_001338429.1:p.Phe237fs frameshift NM_001351501.2:c.710del NP_001338430.1:p.Phe237fs frameshift NM_001351502.2:c.710del NP_001338431.1:p.Phe237fs frameshift NM_006731.2:c.1106del NP_006722.2:p.Phe369fs frameshift NM_006731.2:c.1106delT NR_147213.2:n.1057del non-coding transcript variant NR_147214.2:n.1229del non-coding transcript variant NC_000009.12:g.105619995del NC_000009.11:g.108382276del NG_008754.1:g.66866del LRG_434:g.66866del LRG_434t1:c.1106del LRG_434t2:c.1106del LRG_434p2:p.Phe369fs - Protein change
- F237fs, F369fs, F346fs
- Other names
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- Canonical SPDI
- NC_000009.12:105619988:TTTTTTT:TTTTTT
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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 |
992 | 1042 |
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
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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 (3) |
criteria provided, multiple submitters, no conflicts
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Aug 7, 2023 | RCV000411430.5 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 24, 2024 | RCV000801939.6 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 30, 2023 | RCV003298418.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 30, 2023 | RCV003470343.1 |
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
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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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Likely pathogenic
(Jan 01, 2019)
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criteria provided, single submitter
Method: research
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Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4
Affected status: yes
Allele origin:
germline
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Diagnostics Division, CENTRE FOR DNA FINGERPRINTING AND DIAGNOSTICS
Accession: SCV000924454.1
First in ClinVar: Jun 23, 2019 Last updated: Jun 23, 2019
Comment:
Frameshift variant
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Age: 0-9 years
Geographic origin: India
Tissue: fetus sample after autopsy
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Pathogenic
(Aug 07, 2023)
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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 A, 4
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000698715.2
First in ClinVar: Jan 06, 2017 Last updated: Oct 04, 2023 |
Comment:
Variant summary: FKTN c.1106delT (p.Phe369SerfsX37) results in a premature termination codon and is predicted to cause truncation of the encoded protein, which is a commonly … (more)
Variant summary: FKTN c.1106delT (p.Phe369SerfsX37) results in a premature termination codon and is predicted to cause truncation of the encoded protein, which is a commonly known mechanism for disease. Although the variant is not predicted to cause absence of the protein through nonsense mediated decay, the variant is predicted to disrupt the last 93 amino acids in the protein sequence. Variants downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 2e-05 in 251154 control chromosomes (gnomAD). c.1106delT has been reported in the literature in individuals affected with Walker-Warburg Syndrome (e.g. Aggarwal_2020, Tan_2020, Song_2021, Li_2022). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 31742715, 35843586, 33200426, 32721234). Four ClinVar submitters have assessed the variant since 2014: two classified the variant as likely pathogenic, and two as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Oct 30, 2023)
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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: SCV004197457.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Jan 24, 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: SCV000941744.6
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Phe369Serfs*37) in the FKTN gene. While this is not anticipated to result in nonsense mediated decay, … (more)
This sequence change creates a premature translational stop signal (p.Phe369Serfs*37) in the FKTN gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 93 amino acid(s) of the FKTN protein. This variant is present in population databases (rs750176716, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with FKTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 371091). This variant disrupts a region of the FKTN protein in which other variant(s) (p.Phe390Ilefs*14) have been determined to be pathogenic (PMID: 17878207, 18177472, 18752264, 19266496, 27065010). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Mar 30, 2023)
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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: SCV003993409.2
First in ClinVar: Jul 08, 2023 Last updated: May 01, 2024 |
Comment:
The c.1106delT pathogenic mutation, located in coding exon 8 of the FKTN gene, results from a deletion of one nucleotide at nucleotide position 1106, causing … (more)
The c.1106delT pathogenic mutation, located in coding exon 8 of the FKTN gene, results from a deletion of one nucleotide at nucleotide position 1106, causing a translational frameshift with a predicted alternate stop codon (p.F369Sfs*37). This alteration occurs at the 3' terminus of theFKTN gene, is not expected to trigger nonsense-mediated mRNA decay, and impacts the last 93 amino acids (20%) of the protein. However, premature stop codons are typically deleterious in nature, a significant portion of the protein is affected, and the impacted region is critical for protein function (Ambry internal data). This variant has been reported in the homozygous and compound heterozygous states with other FKTN variants in individuals reported to have features of dystroglycanopathies (Aggarwal S et al. Prenat Diagn, 2020 Jan;40:260-273; Song D et al. Clin Genet, 2021 Mar;99:384-395). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
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Likely pathogenic
(Jun 24, 2016)
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no assertion criteria provided
Method: clinical testing
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Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000486566.2
First in ClinVar: Jan 06, 2017 Last updated: Jun 23, 2019 |
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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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Compound variants of FKTN, POMGNT1, and LAMB1 gene identified by prenatal whole-exome sequencing in three fetuses with congenital hydrocephalus. | Li M | The journal of obstetrics and gynaecology research | 2022 | PMID: 35843586 |
Fetal phenotypes of Mendelian disorders: A descriptive study from India. | Saini N | Prenatal diagnosis | 2022 | PMID: 35587316 |
Genetic variations and clinical spectrum of dystroglycanopathy in a large cohort of Chinese patients. | Song D | Clinical genetics | 2021 | PMID: 33200426 |
Incorporating Spinal Muscular Atrophy Analysis by Next-Generation Sequencing into a Comprehensive Multigene Panel for Neuromuscular Disorders. | Tan CA | Genetic testing and molecular biomarkers | 2020 | PMID: 32721234 |
Exome sequencing for perinatal phenotypes: The significance of deep phenotyping. | Aggarwal S | Prenatal diagnosis | 2020 | PMID: 31742715 |
Analysis of 589,306 genomes identifies individuals resilient to severe Mendelian childhood diseases. | Chen R | Nature biotechnology | 2016 | PMID: 27065010 |
Founder Fukutin mutation causes Walker-Warburg syndrome in four Ashkenazi Jewish families. | Chang W | Prenatal diagnosis | 2009 | PMID: 19266496 |
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 |
Two new patients bearing mutations in the fukutin gene confirm the relevance of this gene in Walker-Warburg syndrome. | Cotarelo RP | Clinical genetics | 2008 | PMID: 18177472 |
Refining genotype phenotype correlations in muscular dystrophies with defective glycosylation of dystroglycan. | Godfrey C | Brain : a journal of neurology | 2007 | PMID: 17878207 |
Text-mined citations for rs750176716 ...
HelpRecord last updated May 01, 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.