ClinVar Genomic variation as it relates to human health
NM_003919.3(SGCE):c.289C>T (p.Arg97Ter)
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_003919.3(SGCE):c.289C>T (p.Arg97Ter)
Variation ID: 5768 Accession: VCV000005768.47
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7q21.3 7: 94628303 (GRCh38) [ NCBI UCSC ] 7: 94257615 (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 Oct 19, 2015 Apr 15, 2024 Nov 22, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_003919.3:c.289C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003910.1:p.Arg97Ter nonsense NM_001099400.2:c.289C>T NP_001092870.1:p.Arg97Ter nonsense NM_001099401.2:c.289C>T NP_001092871.1:p.Arg97Ter nonsense NM_001301139.2:c.166C>T NP_001288068.1:p.Arg56Ter nonsense NM_001346713.2:c.397C>T NP_001333642.1:p.Arg133Ter nonsense NM_001346715.2:c.397C>T NP_001333644.1:p.Arg133Ter nonsense NM_001346717.2:c.289C>T NP_001333646.1:p.Arg97Ter nonsense NM_001346719.2:c.202C>T NP_001333648.1:p.Arg68Ter nonsense NM_001346720.2:c.16C>T NP_001333649.1:p.Arg6Ter nonsense NM_001362807.2:c.202C>T NP_001349736.1:p.Arg68Ter nonsense NM_001362808.2:c.16C>T NP_001349737.1:p.Arg6Ter nonsense NM_001362809.2:c.166C>T NP_001349738.1:p.Arg56Ter nonsense NC_000007.14:g.94628303G>A NC_000007.13:g.94257615G>A NG_008893.2:g.32907C>T LRG_206t1:c.289C>T LRG_206p1:p.Arg97Ter - Protein change
- R97*, R68*, R56*, R6*, R133*
- Other names
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- Canonical SPDI
- NC_000007.14:94628302: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
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00001
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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SGCE | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
66 | 650 | |
CASD1 | - | - |
GRCh38 GRCh37 |
21 | 607 |
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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Pathogenic (7) |
criteria provided, multiple submitters, no conflicts
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Nov 22, 2023 | RCV000006124.28 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Aug 9, 2022 | RCV000713248.23 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 24, 2018 | RCV001267609.4 |
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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Pathogenic
(Nov 17, 2016)
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criteria provided, single submitter
Method: clinical testing
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Dystonia-11, myoclonic
Affected status: yes
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000597025.1
First in ClinVar: Oct 19, 2015 Last updated: Oct 19, 2015 |
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Pathogenic
(Nov 20, 2020)
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criteria provided, single submitter
Method: clinical testing
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Myoclonic dystonia 11
Affected status: unknown
Allele origin:
unknown
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Illumina Laboratory Services, Illumina
Accession: SCV001786644.1
First in ClinVar: Aug 14, 2021 Last updated: Aug 14, 2021 |
Comment:
The SGCE c.289C>T (p.Arg97Ter) variant is a stop-gained variant that is predicted to result in a premature truncation of the protein. Across a selection of … (more)
The SGCE c.289C>T (p.Arg97Ter) variant is a stop-gained variant that is predicted to result in a premature truncation of the protein. Across a selection of the available literature, the p.Arg97Ter variant has been identified in at least four individuals with a myoclonus-dystonia phenotype (Zimprich et al. 2001; O'Riordan et al. 2004; Valente et al. 2005; Grünewald et al. 2008). In addition, this variant segregated with the phenotype in three individuals from a large multigenerational family (Zimprich et al. 2001). This variant is found at a frequency of 0.000009 in the European (non-Finnish) population of the Genome Aggregation Database, though this is based on one allele in a region of good sequencing coverage, so the variant is presumed to be rare. Based on the collective evidence and the application of the ACMG criteria, the p.Arg97Ter variant is classified as pathogenic for myoclonus-dystonia. (less)
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Pathogenic
(Mar 05, 2022)
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criteria provided, single submitter
Method: clinical testing
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Myoclonic dystonia 11
Affected status: yes
Allele origin:
germline
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DASA
Accession: SCV002107117.2
First in ClinVar: Mar 28, 2022 Last updated: Apr 02, 2022 |
Comment:
The c.289C>T;p.(Arg97*) variant creates a premature translational stop signal in the SGCE gene. It is expected to result in an absent or disrupted protein product … (more)
The c.289C>T;p.(Arg97*) variant creates a premature translational stop signal in the SGCE gene. It is expected to result in an absent or disrupted protein product - PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 5768; PMID: 11528394; PMID: 15389977; PMID: 17296918; PMID: 18205193; PMID: 15728306)PS4. The variant is present at low allele frequencies population databases (rs121908489 – gnomAD 0.00004001%; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2_supporting. The variant co-segregated with disease in multiple affected family members (PMID: 11528394) - PP1. In summary, the currently available evidence indicates that the variant is pathogenic (less)
Number of individuals with the variant: 1
Sex: female
Geographic origin: Brazil
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Pathogenic
(Jan 28, 2022)
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criteria provided, single submitter
Method: clinical testing
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Myoclonic dystonia 11
Affected status: yes
Allele origin:
germline
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MGZ Medical Genetics Center
Accession: SCV002581251.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 |
Number of individuals with the variant: 1
Sex: male
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Pathogenic
(Nov 22, 2023)
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criteria provided, single submitter
Method: clinical testing
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Myoclonic dystonia 11
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000761271.6
First in ClinVar: Oct 19, 2015 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg97*) in the SGCE gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg97*) in the SGCE gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SGCE are known to be pathogenic (PMID: 12821748, 15389977, 17853490, 24297365). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individuals with myoclonus-dystonia (PMID: 11528394, 15389977, 15728306, 17296918, 18205193). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 5768). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Nov 01, 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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001247418.20
First in ClinVar: May 12, 2020 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 2
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Pathogenic
(Aug 06, 2018)
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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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Athena Diagnostics Inc
Accession: SCV000843836.1
First in ClinVar: Oct 20, 2018 Last updated: Oct 20, 2018 |
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Pathogenic
(Nov 10, 2021)
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criteria provided, single submitter
Method: clinical testing
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Myoclonic dystonia 11
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
paternal,
germline
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Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München
Accession: SCV001149928.2
First in ClinVar: Feb 03, 2020 Last updated: Dec 24, 2022 |
Observation 1:
Number of individuals with the variant: 1
Clinical Features:
Dystonic disorder (present) , Myoclonus (present)
Observation 2:
Number of individuals with the variant: 1
Clinical Features:
Dystonic disorder (present) , Myoclonus (present)
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Pathogenic
(Apr 24, 2018)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: yes
Allele origin:
germline
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Ambry Genetics
Accession: SCV001445791.2
First in ClinVar: Nov 21, 2020 Last updated: Jan 07, 2023 |
Number of individuals with the variant: 1
Clinical Features:
Delayed speech and language development (present) , Chorea (present) , Dysmetria (present) , Anxiety (present) , Tremor (present) , Tics (present) , Headache (present) , … (more)
Delayed speech and language development (present) , Chorea (present) , Dysmetria (present) , Anxiety (present) , Tremor (present) , Tics (present) , Headache (present) , Obstructive sleep apnea syndrome (present) , Photophobia (present) , Muscular hypotonia (present) , Specific learning disability (present) , Arnold-Chiari type I malformation (present) (less)
Sex: male
Ethnicity/Population group: Caucasian/Irish/English
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Pathogenic
(Aug 09, 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: SCV000890333.4
First in ClinVar: Mar 19, 2019 Last updated: Mar 04, 2023 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 18175340, 27363292, 17702043, 19117362, 23332219, 19261534, 25525159, 11528394, 18355305, 18205193, 15728306, 15389977, 23748201, 33098801, 35041927, 9750929, 17296918) (less)
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Pathogenic
(Feb 22, 2005)
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no assertion criteria provided
Method: literature only
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DYSTONIA 11, MYOCLONIC
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000026306.2
First in ClinVar: Apr 04, 2013 Last updated: Oct 19, 2015 |
Comment on evidence:
In affected members of a family with myoclonus-dystonia syndrome (DYT11; 159900), Zimprich et al. (2001) found an arg97-to-ter (R97X) nonsense mutation in exon 3 of … (more)
In affected members of a family with myoclonus-dystonia syndrome (DYT11; 159900), Zimprich et al. (2001) found an arg97-to-ter (R97X) nonsense mutation in exon 3 of the SGCE gene. Valente et al. (2005) identified the R97X mutation in 2 of 58 unrelated patients with a range of myoclonic/dystonic syndromes. Both patients had a phenotype consistent with myoclonus-dystonia syndrome. (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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Myoclonus-dystonia and epilepsy in a family with a novel epsilon-sarcoglycan mutation. | Haugarvoll K | Journal of neurology | 2014 | PMID: 24297365 |
Primary Myoclonus-Dystonia: A Diagnosis Often Missed in Children. | Ghosh D | Journal of child neurology | 2013 | PMID: 23748201 |
Myoclonus-dystonia: significance of large SGCE deletions. | Grünewald A | Human mutation | 2008 | PMID: 18205193 |
Myoclonus-dystonia syndrome: clinical presentation, disease course, and genetic features in 11 families. | Nardocci N | Movement disorders : official journal of the Movement Disorder Society | 2008 | PMID: 17853490 |
Myoclonus-dystonia, obsessive-compulsive disorder, and alcohol dependence in SGCE mutation carriers. | Hess CW | Neurology | 2007 | PMID: 17296918 |
The epsilon-sarcoglycan gene in myoclonic syndromes. | Valente EM | Neurology | 2005 | PMID: 15728306 |
Inherited myoclonus-dystonia and epilepsy: further evidence of an association? | O'Riordan S | Movement disorders : official journal of the Movement Disorder Society | 2004 | PMID: 15389977 |
Hereditary myoclonus-dystonia associated with epilepsy. | Foncke EM | Neurology | 2003 | PMID: 12821748 |
Mutations in the gene encoding epsilon-sarcoglycan cause myoclonus-dystonia syndrome. | Zimprich A | Nature genetics | 2001 | PMID: 11528394 |
Inherited myoclonus-dystonia syndrome. | Gasser T | Advances in neurology | 1998 | PMID: 9750929 |
Text-mined citations for rs121908489 ...
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.