ClinVar Genomic variation as it relates to human health
NM_001927.4(DES):c.735+1G>A
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_001927.4(DES):c.735+1G>A
Variation ID: 44268 Accession: VCV000044268.19
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2q35 2: 219420347 (GRCh38) [ NCBI UCSC ] 2: 220285069 (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 Feb 28, 2024 May 20, 2019 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001927.4:c.735+1G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice donor NM_001382708.1:c.732+1G>A splice donor NM_001382709.1:c.735+1G>A splice donor NM_001382710.1:c.735+1G>A splice donor NM_001382711.1:c.735+1G>A splice donor NM_001382712.1:c.735+1G>A splice donor NM_001382713.1:c.496-178G>A intron variant NC_000002.12:g.219420347G>A NC_000002.11:g.220285069G>A NG_008043.1:g.6971G>A LRG_380:g.6971G>A LRG_380t1:c.735+1G>A - Protein change
- Other names
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- Canonical SPDI
- NC_000002.12:219420346:G:A
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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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DES | - | - |
GRCh38 GRCh37 |
1044 | 1088 |
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 (1) |
criteria provided, single submitter
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Jun 23, 2016 | RCV000393713.14 | |
Pathogenic/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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May 20, 2019 | RCV001220792.15 |
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
(Jun 23, 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: SCV000343204.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
Number of individuals with the variant: 1
Sex: mixed
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Likely pathogenic
(May 22, 2017)
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criteria provided, single submitter
Method: clinical testing
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Desmin-related myofibrillar myopathy
(Autosomal dominant inheritance)
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000060906.5
First in ClinVar: May 03, 2013 Last updated: Apr 09, 2018 |
Comment:
The c.735+1G>A variant in DES has been reported in at least 2 individuals with d esminopathy (Shatunov et al., unpublished data; reviewed by Goldfarb 2004, … (more)
The c.735+1G>A variant in DES has been reported in at least 2 individuals with d esminopathy (Shatunov et al., unpublished data; reviewed by Goldfarb 2004, Gudko va 2013, LMM data), and was absent from large population studies. This variant o ccurs in the invariant region (+/- 1,2) of the splice consensus sequence and is predicted to cause altered splicing leading to an abnormal or absent protein. Ad ditional variants affecting splicing of this exon have been reported in individu als with desminopathy including a different variant at the same position (c.7351 +G>C LMM data: variant occurred de novo) and c.735+3A>G (identified in 6 individ uals with desminopathy and segregated in 9 individuals from 2 families: Park 200 0, Dalakas 2000, Wahni 2012, Greenberg 2012, McDonald 2012, Gudkova 2013, LMM un published data). In summary, although additional studies are required to fully e stablish its clinical significance, the c.735+1G>A variant is likely pathogenic. (less)
Number of individuals with the variant: 3
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Pathogenic
(May 20, 2019)
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criteria provided, single submitter
Method: clinical testing
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Desmin-related myofibrillar myopathy
Desmin-related myofibrillar myopathy
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001392803.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 28, 2024 |
Comment:
Disruption of this splice site has been observed in several individuals affected with clinical features of autosomal dominant desminopathy (PMID: 30614851, 28703267). ClinVar contains an … (more)
Disruption of this splice site has been observed in several individuals affected with clinical features of autosomal dominant desminopathy (PMID: 30614851, 28703267). ClinVar contains an entry for this variant (Variation ID: 44268). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 3 of the DES gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 29034897). For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in DES are known to be pathogenic (PMID: 23575897). (less)
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Likely pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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Desmin-related myofibrillar myopathy
Affected status: yes
Allele origin:
germline
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Genomics England Pilot Project, Genomics England
Accession: SCV001760073.1
First in ClinVar: Jul 27, 2021 Last updated: Jul 27, 2021 |
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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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A novel phenotype with splicing mutation identified in a Chinese family with desminopathy. | Fan P | Chinese medical journal | 2019 | PMID: 30614851 |
Generation of iPSC line from desmin-related cardiomyopathy patient carrying splice site mutation of DES gene. | Khudiakov A | Stem cell research | 2017 | PMID: 29034897 |
Restrictive cardiomyopathy due to novel desmin gene mutation. | Ojrzyńska N | Kardiologia polska | 2017 | PMID: 28703267 |
Recessive desmin-null muscular dystrophy with central nuclei and mitochondrial abnormalities. | Henderson M | Acta neuropathologica | 2013 | PMID: 23575897 |
Diagnostic challenge in desmin cardiomyopathy with transformation of clinical phenotypes. | Gudkova A | Pediatric cardiology | 2013 | PMID: 22484823 |
Splicing in action: assessing disease causing sequence changes. | Baralle D | Journal of medical genetics | 2005 | PMID: 16199547 |
Desmin myopathy. | Goldfarb LG | Brain : a journal of neurology | 2004 | PMID: 14724127 |
Desmin splice variants causing cardiac and skeletal myopathy. | Park KY | Journal of medical genetics | 2000 | PMID: 11073539 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DES | - | - | - | - |
Text-mined citations for rs397516698 ...
HelpRecord last updated Apr 20, 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.