ClinVar Genomic variation as it relates to human health
NM_144573.4(NEXN):c.1401AGA[2] (p.Glu470del)
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_144573.4(NEXN):c.1401AGA[2] (p.Glu470del)
Variation ID: 47890 Accession: VCV000047890.19
- Type and length
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Microsatellite, 3 bp
- Location
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Cytogenetic: 1p31.1 1: 77935972-77935974 (GRCh38) [ NCBI UCSC ] 1: 78401657-78401659 (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 May 29, 2016 Feb 4, 2024 Jun 1, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_144573.4:c.1401AGA[2] MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_653174.3:p.Glu470del inframe deletion NM_144573.4:c.1407_1409del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_001172309.2:c.1209AGA[2] NP_001165780.1:p.Glu406del inframe deletion NM_144573.3:c.1405_1407delGAA NM_144573.3:c.1407_1409delAGA NC_000001.11:g.77935972AGA[2] NC_000001.10:g.78401657AGA[2] NG_016625.1:g.52458AGA[2] LRG_442:g.52458AGA[2] LRG_442t1:c.1407_1409del - Protein change
- E470del, E406del
- Other names
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- Canonical SPDI
- NC_000001.11:77935971:AGAAGAAGA:AGAAGA
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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
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
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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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NEXN | - | - |
GRCh38 GRCh37 |
614 | 693 |
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
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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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Uncertain significance (1) |
criteria provided, single submitter
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Feb 10, 2015 | RCV000041160.7 | |
Uncertain significance (1) |
criteria provided, single submitter
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Feb 9, 2016 | RCV000240639.2 | |
Uncertain significance (1) |
no assertion criteria provided
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May 1, 2016 | RCV000491718.2 | |
Uncertain significance (1) |
criteria provided, single submitter
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Dec 1, 2020 | RCV000621584.2 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Oct 3, 2022 | RCV000701648.5 | |
Uncertain significance (3) |
criteria provided, multiple submitters, no conflicts
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Jun 1, 2023 | RCV001256889.7 |
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
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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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Uncertain significance
(Feb 10, 2015)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000064851.6
First in ClinVar: May 03, 2013 Last updated: Aug 26, 2019 |
Comment:
The p.Glu470del variant in NEXN has been identified by our laboratory in 1 infan t with DCM, 1 adult with LVNC (Pugh 2014), and 1 … (more)
The p.Glu470del variant in NEXN has been identified by our laboratory in 1 infan t with DCM, 1 adult with LVNC (Pugh 2014), and 1 adult with HCM who carried a pa thogenic variant in another gene that was sufficient to explain the disease. Thi s variant has also been identified in 4/16472 of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs3975 17846). This variant is a deletion of a single amino acid at position 470 and do es not alter the protein reading-frame. It is unclear if this deletion will impa ct protein function. In summary, the clinical significance of the p.Glu470del va riant is uncertain. (less)
Number of individuals with the variant: 3
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Uncertain significance
(Oct 03, 2022)
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criteria provided, single submitter
Method: clinical testing
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Dilated cardiomyopathy 1CC
Hypertrophic cardiomyopathy 20
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000830459.4
First in ClinVar: Oct 10, 2018 Last updated: Feb 07, 2023 |
Comment:
This variant, c.1407_1409del, results in the deletion of 1 amino acid(s) of the NEXN protein (p.Glu470del), but otherwise preserves the integrity of the reading frame. … (more)
This variant, c.1407_1409del, results in the deletion of 1 amino acid(s) of the NEXN protein (p.Glu470del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs762929322, gnomAD 0.02%). This variant has been observed in individual(s) with dilated cardiomyopathy (PMID: 24503780, 27532257). ClinVar contains an entry for this variant (Variation ID: 47890). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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
(Jun 01, 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: SCV001790626.2
First in ClinVar: Aug 21, 2021 Last updated: Jun 24, 2023 |
Comment:
Identified in patients with DCM in the published literature (Pugh et al., 2014; Walsh et al., 2017); In-frame deletion of a single glutamic acid residue; … (more)
Identified in patients with DCM in the published literature (Pugh et al., 2014; Walsh et al., 2017); In-frame deletion of a single glutamic acid residue; In silico analysis supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27532257, 24503780) (less)
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Uncertain significance
(Jul 15, 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: SCV003813616.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Uncertain significance
(Feb 09, 2016)
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criteria provided, single submitter
Method: clinical testing
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Dilated cardiomyopathy 1CC
Affected status: yes
Allele origin:
germline
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Center for Medical Genetics Ghent, University of Ghent
Accession: SCV000299267.2
First in ClinVar: Sep 10, 2016 Last updated: Aug 04, 2018 |
Comment:
This variant has not been identified in large population databases (Gnomad, 1000 Genomes, Go NL, Exome Variant Server). The variant results in an inframe deletion … (more)
This variant has not been identified in large population databases (Gnomad, 1000 Genomes, Go NL, Exome Variant Server). The variant results in an inframe deletion of one amino acid and thus reduces the length of the protein. (less)
Sex: female
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Uncertain significance
(May 21, 2020)
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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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Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute
Accession: SCV001433386.1
First in ClinVar: Sep 27, 2020 Last updated: Sep 27, 2020 |
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Uncertain significance
(Dec 01, 2020)
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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: SCV000739980.4
First in ClinVar: Apr 14, 2018 Last updated: Nov 29, 2022 |
Comment:
The c.1407_1409delAGA variant (also known as p.E470del) is located in coding exon 10 of the NEXN gene. This variant results from an in-frame AGA deletion … (more)
The c.1407_1409delAGA variant (also known as p.E470del) is located in coding exon 10 of the NEXN gene. This variant results from an in-frame AGA deletion at nucleotide positions 1407 to 1409. This results in the in-frame deletion of a glutamic acid at codon 470. This variant was reported in 1 individual with dilated cardiomyopathy (DCM) who also had variants in other cardiac-related genes and in one individual from a DCM genetic testing cohort; however, clinical details were limited, and reports may overlap (Pugh TJ et al. Genet. Med. 2014;16:601-8; Walsh R et al. Genet. Med., 2017 02;19:192-203). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
Number of individuals with the variant: 1
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Uncertain significance
(Nov 14, 2021)
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criteria provided, single submitter
Method: clinical testing
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Dilated cardiomyopathy 1CC
Hypertrophic cardiomyopathy 20
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002780369.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Uncertain significance
(May 01, 2016)
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no assertion criteria provided
Method: clinical testing
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Arrhythmogenic right ventricular dysplasia 9
Affected status: yes
Allele origin:
germline
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Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen
Accession: SCV000298157.1
First in ClinVar: Jun 25, 2017 Last updated: Jun 25, 2017 |
Number of individuals with the variant: 1
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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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Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples. | Walsh R | Genetics in medicine : official journal of the American College of Medical Genetics | 2017 | PMID: 27532257 |
The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing. | Pugh TJ | Genetics in medicine : official journal of the American College of Medical Genetics | 2014 | PMID: 24503780 |
Text-mined citations for rs397517846 ...
HelpRecord last updated Mar 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.