ClinVar Genomic variation as it relates to human health
NM_001079802.2(FKTN):c.820C>T (p.Arg274Trp)
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.
Likely pathogenic(1); Uncertain significance(9)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001079802.2(FKTN):c.820C>T (p.Arg274Trp)
Variation ID: 290479 Accession: VCV000290479.32
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 9q31.2 9: 105615317 (GRCh38) [ NCBI UCSC ] 9: 108377598 (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 Dec 6, 2016 May 12, 2024 Nov 28, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001079802.2:c.820C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001073270.1:p.Arg274Trp missense NM_001198963.2:c.820C>T NP_001185892.1:p.Arg274Trp missense NM_001351496.2:c.820C>T NP_001338425.1:p.Arg274Trp missense NM_001351497.2:c.751C>T NP_001338426.1:p.Arg251Trp missense NM_001351498.2:c.820C>T NP_001338427.1:p.Arg274Trp missense NM_001351499.2:c.424C>T NP_001338428.1:p.Arg142Trp missense NM_001351500.2:c.424C>T NP_001338429.1:p.Arg142Trp missense NM_001351501.2:c.424C>T NP_001338430.1:p.Arg142Trp missense NM_001351502.2:c.424C>T NP_001338431.1:p.Arg142Trp missense NM_006731.2:c.820C>T NP_006722.2:p.Arg274Trp missense NR_147214.2:n.943C>T non-coding transcript variant NC_000009.12:g.105615317C>T NC_000009.11:g.108377598C>T NG_008754.1:g.62188C>T LRG_434:g.62188C>T LRG_434t1:c.820C>T LRG_434p1:p.Arg274Trp LRG_434t2:c.820C>T LRG_434p2:p.Arg274Trp - Protein change
- R274W, R251W, R142W
- Other names
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- Canonical SPDI
- NC_000009.12:105615316:C:T
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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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0.00020 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00009
Exome Aggregation Consortium (ExAC) 0.00010
1000 Genomes Project 30x 0.00016
1000 Genomes Project 0.00020
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
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. |
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FKTN | - | - |
GRCh38 GRCh37 |
992 | 1042 |
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. |
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Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Jul 1, 2021 | RCV000263255.19 | |
Uncertain significance (2) |
criteria provided, single submitter
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Mar 9, 2022 | RCV000526522.6 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jan 12, 2018 | RCV001169710.5 | |
Uncertain significance (3) |
criteria provided, multiple submitters, no conflicts
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Nov 28, 2023 | RCV001169711.7 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jan 7, 2021 | RCV002429237.3 | |
Uncertain significance (1) |
criteria provided, single submitter
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Sep 14, 2021 | RCV002487283.2 |
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. |
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Uncertain significance
(Sep 26, 2016)
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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: SCV000345042.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
Number of individuals with the variant: 1
Sex: mixed
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Uncertain significance
(Jan 12, 2018)
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criteria provided, single submitter
Method: clinical testing
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Dilated cardiomyopathy 1X
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001332474.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
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Uncertain significance
(Jan 12, 2018)
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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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Illumina Laboratory Services, Illumina
Accession: SCV001332475.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
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Uncertain significance
(Apr 10, 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 A, 4
Affected status: unknown
Allele origin:
inherited
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New York Genome Center
Study: CSER-NYCKidSeq
Accession: SCV002099063.1 First in ClinVar: Feb 26, 2022 Last updated: Feb 26, 2022 |
Clinical Features:
Global developmental delay (present) , Intellectual disability (present) , Congenital nystagmus (present) , Ventricular septal defect (present) , Hypotonia (present) , Hypertonia (present) , Failure … (more)
Global developmental delay (present) , Intellectual disability (present) , Congenital nystagmus (present) , Ventricular septal defect (present) , Hypotonia (present) , Hypertonia (present) , Failure to thrive (present) , Congenital laryngomalacia (present) (less)
Secondary finding: no
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Uncertain significance
(Sep 14, 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: SCV002779107.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Uncertain significance
(Mar 09, 2022)
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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: SCV000630822.3
First in ClinVar: Dec 26, 2017 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 274 of the FKTN protein … (more)
This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 274 of the FKTN protein (p.Arg274Trp). This variant is present in population databases (rs558187116, gnomAD 0.04%). This missense change has been observed in individual(s) with clinical features of FKTN-related conditions (PMID: 31983221). ClinVar contains an entry for this variant (Variation ID: 290479). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C35"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
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Uncertain significance
(Jan 07, 2021)
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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: SCV002681239.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.R274W variant (also known as c.820C>T), located in coding exon 6 of the FKTN gene, results from a C to T substitution at nucleotide … (more)
The p.R274W variant (also known as c.820C>T), located in coding exon 6 of the FKTN gene, results from a C to T substitution at nucleotide position 820. The arginine at codon 274 is replaced by tryptophan, an amino acid with dissimilar properties. This variant has been detected in a dilated cardiomyopathy cohort; however, details were limited (Mazzarotto F et al. Circulation, 2020 02;141:387-398). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
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Likely pathogenic
(Jul 01, 2021)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV002564058.11
First in ClinVar: Aug 23, 2022 Last updated: May 12, 2024 |
Number of individuals with the variant: 1
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Uncertain significance
(Nov 28, 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
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
unknown
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV004175980.1
First in ClinVar: Dec 17, 2023 Last updated: Dec 17, 2023 |
Comment:
Criteria applied: PM3,PM2_SUP,PP3
Clinical Features:
Intellectual disability (present) , Elevated circulating creatine kinase concentration (present) , Obesity (present)
Sex: male
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Uncertain significance
(Sep 09, 2019)
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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: SCV003832666.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Uncertain significance
(Feb 21, 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: SCV002079601.1
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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Reevaluating the Genetic Contribution of Monogenic Dilated Cardiomyopathy. | Mazzarotto F | Circulation | 2020 | PMID: 31983221 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=FKTN | - | - | - | - |
Text-mined citations for rs558187116 ...
HelpRecord last updated May 12, 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.