ClinVar Genomic variation as it relates to human health
NM_001927.4(DES):c.1286G>A (p.Arg429Gln)
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.1286G>A (p.Arg429Gln)
Variation ID: 289962 Accession: VCV000289962.20
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2q35 2: 219423818 (GRCh38) [ NCBI UCSC ] 2: 220288540 (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 Apr 14, 2018 Feb 28, 2024 Oct 17, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001927.4:c.1286G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001918.3:p.Arg429Gln missense NC_000002.12:g.219423818G>A NC_000002.11:g.220288540G>A NG_008043.1:g.10442G>A LRG_380:g.10442G>A LRG_380t1:c.1286G>A - Protein change
- R429Q
- Other names
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- Canonical SPDI
- NC_000002.12:219423817: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.
Trans-Omics for Precision Medicine (TOPMed) 0.00004
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
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 |
1042 | 1086 |
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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Uncertain significance (3) |
criteria provided, multiple submitters, no conflicts
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May 24, 2022 | RCV000357490.11 | |
Uncertain significance (1) |
criteria provided, single submitter
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Oct 17, 2023 | RCV000694336.7 | |
Uncertain significance (1) |
criteria provided, single submitter
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Oct 18, 2022 | RCV000617457.2 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jul 28, 2021 | RCV002487276.1 | |
Uncertain significance (1) |
criteria provided, single submitter
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Mar 1, 2023 | RCV003226276.1 |
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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Uncertain significance
(Sep 26, 2017)
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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: SCV000344431.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 2
Sex: mixed
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Uncertain significance
(Oct 18, 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: SCV000737286.4
First in ClinVar: Apr 14, 2018 Last updated: Nov 29, 2022 |
Comment:
The p.R429Q variant (also known as c.1286G>A), located in coding exon 7 of the DES gene, results from a G to A substitution at nucleotide … (more)
The p.R429Q variant (also known as c.1286G>A), located in coding exon 7 of the DES gene, results from a G to A substitution at nucleotide position 1286. The arginine at codon 429 is replaced by glutamine, an amino acid with highly similar properties. This variant has been reported in hypertrophic cardiomyopathy cohorts and co-occurred with variants in other cardiac-related genes; however, clinical details were limited in some cases (Lopes LR et al. J Med Genet, 2013 Apr;50:228-39; Thomson KL et al. Genet Med, 2019 07;21:1576-1584; Limongelli G et al. Genes (Basel), 2020 05;11:[ePub ahead of print]). This amino acid position is highly 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)
Number of individuals with the variant: 1
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Uncertain significance
(Jul 28, 2021)
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criteria provided, single submitter
Method: clinical testing
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Neurogenic scapuloperoneal syndrome, Kaeser type
Desmin-related myofibrillar myopathy Dilated cardiomyopathy 1I
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002787856.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Uncertain significance
(May 24, 2022)
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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: SCV001826225.3
First in ClinVar: Sep 08, 2021 Last updated: Mar 04, 2023 |
Comment:
Reported previously as a likely pathogenic, maternally inherited heterozygous variant in a patient with suspected ARVC; however, the patient also had compound heterozygous variants in … (more)
Reported previously as a likely pathogenic, maternally inherited heterozygous variant in a patient with suspected ARVC; however, the patient also had compound heterozygous variants in another gene and it was thought that all three variants caused a more severe phenotype. The mother was reported to be unaffected (Limongelli et al., 2020); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25351510, 23396983, 26807690, 32397162) (less)
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Uncertain significance
(Mar 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV003922857.1
First in ClinVar: May 13, 2023 Last updated: May 13, 2023 |
Comment:
Variant summary: DES c.1286G>A (p.Arg429Gln) results in a conservative amino acid change in the encoded protein sequence, altering a highly conserved residue (HGMD). Three of … (more)
Variant summary: DES c.1286G>A (p.Arg429Gln) results in a conservative amino acid change in the encoded protein sequence, altering a highly conserved residue (HGMD). Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 5.2e-05 in 251480 control chromosomes. The observed variant frequency is slightly greater than estimated maximal expected allele frequency for a pathogenic variant in DES causing Dilated Cardiomyopathy phenotype (3.1e-05), suggesting that the variant is benign polymorphism. c.1286G>A has been reported in the literature in individuals affected with Cardiomyopathy without evidence of cosegregation (Lopes_2013, Thomson_2019, Limongelli_2020, Sepp_2022). These reports do not provide unequivocal conclusions about association of the variant with Dilated Cardiomyopathy. Co-occurrences with other pathogenic variants have been reported among these individuals (MYH7 c.2389G>A, p.Ala797Thr; PKP2 c.368G>A, p.Trp123Ter), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five submitters have provided clinical-significance assessments for this variant to ClinVar after 2014, and all classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. (less)
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Uncertain significance
(Feb 25, 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: SCV003829018.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Uncertain significance
(Oct 17, 2023)
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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: SCV000822776.7
First in ClinVar: Oct 10, 2018 Last updated: Feb 28, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 429 of the DES protein (p.Arg429Gln). … (more)
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 429 of the DES protein (p.Arg429Gln). This variant is present in population databases (rs200580581, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of autosomal dominant DES-related conditions (PMID: 23396983, 32397162). ClinVar contains an entry for this variant (Variation ID: 289962). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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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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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The Genetic Architecture of Hypertrophic Cardiomyopathy in Hungary: Analysis of 242 Patients with a Panel of 98 Genes. | Sepp R | Diagnostics (Basel, Switzerland) | 2022 | PMID: 35626289 |
Genotype-Phenotype Correlation: A Triple DNA Mutational Event in a Boy Entering Sport Conveys an Additional Pathogenicity Risk. | Limongelli G | Genes | 2020 | PMID: 32397162 |
Analysis of 51 proposed hypertrophic cardiomyopathy genes from genome sequencing data in sarcomere negative cases has negligible diagnostic yield. | Thomson KL | Genetics in medicine : official journal of the American College of Medical Genetics | 2019 | PMID: 30531895 |
Genetic complexity in hypertrophic cardiomyopathy revealed by high-throughput sequencing. | Lopes LR | Journal of medical genetics | 2013 | PMID: 23396983 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DES | - | - | - | - |
Text-mined citations for rs200580581 ...
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.