This frameshifting variant in exon 5 of 12 introduces a premature stop codon and is therefore predicted to result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay (NMD). This alteration has been identified in at least three individuals with myoclonus-dystonia (M-D) (PMID: 32775037, 28869676). In addition, a different frameshift variant leading to a protein truncation at the same codon 218, c.623delG (p.Gly208Valfs*11), was identified in an individual with myoclonus-dystonia syndrome and prominent psychiatric comorbidities (PMID: 29429788). Furthermore, a nearby frameshift variant, c.619_620delAG (p.Arg207Glyfs*9), was reported in a large M-D family where all the affected individuals inherited the alteration from the father, indicating maternal imprinting and paternal expression (PMID: 16534121, 17101905, 19506430). The c.619del (p.Arg207GlyfsTer12) is absent from the gnomAD population database and thus is presumed to be rare. Based on the available evidence, the c.619del (p.Arg207GlyfsTer12) variant is classified as Pathogenic.
ClinVar Genomic variation as it relates to human health
NM_003919.3(SGCE):c.619del (p.Arg207fs)
Germline
Classification
Help
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.
(6)
Help
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.
Pathogenic
6
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_003919.3(SGCE):c.619del (p.Arg207fs)
Variation ID: 448358 Accession: VCV000448358.10
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 7q21.3 7: 94618801 (GRCh38) [ NCBI UCSC ] 7: 94248113 (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 19, 2017 Feb 28, 2024 May 23, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_003919.3:c.619del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003910.1:p.Arg207fs frameshift NM_001099400.2:c.619del NP_001092870.1:p.Arg207fs frameshift NM_001099401.2:c.619del NP_001092871.1:p.Arg207fs frameshift NM_001301139.2:c.496del NP_001288068.1:p.Arg166fs frameshift NM_001346713.2:c.727del NP_001333642.1:p.Arg243fs frameshift NM_001346715.2:c.727del NP_001333644.1:p.Arg243fs frameshift NM_001346717.2:c.619del NP_001333646.1:p.Arg207fs frameshift NM_001346719.2:c.532del NP_001333648.1:p.Arg178fs frameshift NM_001346720.2:c.346del NP_001333649.1:p.Arg116fs frameshift NM_001362807.2:c.532del NP_001349736.1:p.Arg178fs frameshift NM_001362808.2:c.346del NP_001349737.1:p.Arg116fs frameshift NM_001362809.2:c.496del NP_001349738.1:p.Arg166fs frameshift NM_003919.2:c.619del NM_003919.2:c.619delA NC_000007.14:g.94618801del NC_000007.13:g.94248113del NG_008893.2:g.42409del LRG_206t1:c.619del LRG_206p1:p.Arg207fs - Protein change
- R116fs, R178fs, R166fs, R207fs, R243fs
- Other names
- -
- Canonical SPDI
- NC_000007.14:94618800: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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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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- Links
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 | ||
|---|---|---|---|---|---|---|
| HI score
Help
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. |
|||
| SGCE | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
67 | 661 | |
| CASD1 | - | - |
GRCh38 GRCh37 |
33 | 629 | |
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. |
|---|---|---|---|---|
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Oct 13, 2022 | RCV000516288.3 | |
| Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
May 23, 2023 | RCV000534756.13 |
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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|---|---|---|---|---|---|
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Pathogenic
(Dec 12, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Athena Diagnostics
Accession: SCV000615227.1
First in ClinVar: Dec 19, 2017 Last updated: Dec 19, 2017 |
|
|
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Pathogenic
(May 07, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Myoclonic dystonia 11
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
paternal
|
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München
Accession: SCV001149926.1
First in ClinVar: Feb 03, 2020 Last updated: Feb 03, 2020 |
Sex: male
Tissue: blood
|
|
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Pathogenic
(Aug 12, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
DYSTONIA 11, MYOCLONIC
Affected status: yes
Allele origin:
germline
|
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego
Accession: SCV001984825.1
First in ClinVar: Oct 30, 2021 Last updated: Oct 30, 2021 |
Comment:
This frameshifting variant in exon 5 of 12 introduces a premature stop codon and is therefore predicted to result in loss of normal protein function … (more)
This frameshifting variant in exon 5 of 12 introduces a premature stop codon and is therefore predicted to result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay (NMD). This alteration has been identified in at least three individuals with myoclonus-dystonia (M-D) (PMID: 32775037, 28869676). In addition, a different frameshift variant leading to a protein truncation at the same codon 218, c.623delG (p.Gly208Valfs*11), was identified in an individual with myoclonus-dystonia syndrome and prominent psychiatric comorbidities (PMID: 29429788). Furthermore, a nearby frameshift variant, c.619_620delAG (p.Arg207Glyfs*9), was reported in a large M-D family where all the affected individuals inherited the alteration from the father, indicating maternal imprinting and paternal expression (PMID: 16534121, 17101905, 19506430). The c.619del (p.Arg207GlyfsTer12) is absent from the gnomAD population database and thus is presumed to be rare. Based on the available evidence, the c.619del (p.Arg207GlyfsTer12) variant is classified as Pathogenic. (less)
|
|
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Pathogenic
(Oct 13, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV003918316.1
First in ClinVar: Apr 23, 2023 Last updated: Apr 23, 2023 |
Comment:
Frameshift 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)
Frameshift 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: 32775037, 33098801) (less)
|
|
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Pathogenic
(May 23, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Myoclonic dystonia 11
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV003925752.1
First in ClinVar: May 27, 2023 Last updated: May 27, 2023 |
Clinical Features:
Dystonic disorder (present) , Paroxysmal dystonia (present) , Paroxysmal dyskinesia (present) , Dyskinesia (present)
|
|
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Pathogenic
(Apr 26, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Myoclonic dystonia 11
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000638422.4
First in ClinVar: Dec 26, 2017 Last updated: Feb 28, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 448358). This premature translational stop signal … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 448358). This premature translational stop signal has been observed in individual(s) with clinical features of idiopathic generalized epilepsy (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg207Glyfs*12) 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). (less)
|
Comment:
Comment:
Frameshift 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: 32775037, 33098801)
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 448358). This premature translational stop signal has been observed in individual(s) with clinical features of idiopathic generalized epilepsy (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg207Glyfs*12) 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).
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. |
Comment:
This frameshifting variant in exon 5 of 12 introduces a premature stop codon and is therefore predicted to result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay (NMD). This alteration has been identified in at least three individuals with myoclonus-dystonia (M-D) (PMID: 32775037, 28869676). In addition, a different frameshift variant leading to a protein truncation at the same codon 218, c.623delG (p.Gly208Valfs*11), was identified in an individual with myoclonus-dystonia syndrome and prominent psychiatric comorbidities (PMID: 29429788). Furthermore, a nearby frameshift variant, c.619_620delAG (p.Arg207Glyfs*9), was reported in a large M-D family where all the affected individuals inherited the alteration from the father, indicating maternal imprinting and paternal expression (PMID: 16534121, 17101905, 19506430). The c.619del (p.Arg207GlyfsTer12) is absent from the gnomAD population database and thus is presumed to be rare. Based on the available evidence, the c.619del (p.Arg207GlyfsTer12) variant is classified as Pathogenic.
Comment:
Frameshift 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: 32775037, 33098801)
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 448358). This premature translational stop signal has been observed in individual(s) with clinical features of idiopathic generalized epilepsy (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg207Glyfs*12) 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).
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Myoclonus-dystonia and epilepsy in a family with a novel epsilon-sarcoglycan mutation. | Haugarvoll K | Journal of neurology | 2014 | PMID: 24297365 |
| 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 |
| 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 |
Text-mined citations for rs1554352819 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Sep 29, 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.