NM_003919.3(SGCE):c.619del (p.Arg207fs) AND Myoclonic dystonia 11

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: May 23, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000534756.12

Allele description

NM_003919.3(SGCE):c.619del (p.Arg207fs)

Genes:

CASD1:CAS1 domain containing 1 [Gene - OMIM - HGNC]
SGCE:sarcoglycan epsilon [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

7q21.3

Genomic location:

Preferred name:

NM_003919.3(SGCE):c.619del (p.Arg207fs)

HGVS:

NC_000007.14:g.94618801del
NG_008893.2:g.42409del
NM_001099400.2:c.619del
NM_001099401.2:c.619del
NM_001301139.2:c.496del
NM_001346713.2:c.727del
NM_001346715.2:c.727del
NM_001346717.2:c.619del
NM_001346719.2:c.532del
NM_001346720.2:c.346del
NM_001362807.2:c.532del
NM_001362808.2:c.346del
NM_001362809.2:c.496del
NM_003919.2:c.619del
NM_003919.3:c.619delMANE SELECT
NP_001092870.1:p.Arg207fs
NP_001092871.1:p.Arg207fs
NP_001288068.1:p.Arg166fs
NP_001333642.1:p.Arg243fs
NP_001333644.1:p.Arg243fs
NP_001333646.1:p.Arg207fs
NP_001333648.1:p.Arg178fs
NP_001333649.1:p.Arg116fs
NP_001349736.1:p.Arg178fs
NP_001349737.1:p.Arg116fs
NP_001349738.1:p.Arg166fs
NP_003910.1:p.Arg207fs
LRG_206t1:c.619del
LRG_206p1:p.Arg207fs
NC_000007.13:g.94248113del
NM_003919.2:c.619delA
p.Arg207Glyfs*12

Protein change:

R116fs

Links:

dbSNP: rs1554352819

NCBI 1000 Genomes Browser:

rs1554352819

Molecular consequence:

NM_001099400.2:c.619del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001099401.2:c.619del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001301139.2:c.496del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001346713.2:c.727del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001346715.2:c.727del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001346717.2:c.619del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001346719.2:c.532del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001346720.2:c.346del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001362807.2:c.532del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001362808.2:c.346del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001362809.2:c.496del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003919.3:c.619del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Myoclonic dystonia 11 (DYT11)
Synonyms:: Myoclonic dystonia; Dystonia 11; Dystonia, alcohol responsive; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008044; MedGen: C1834570; Orphanet: 36899; OMIM: 159900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000638422	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 26, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 12821748, 15389977, 17853490, 24297365, 28492532
SCV001149926	Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	criteria provided, single submitter (Classification criteria August 2017)	Pathogenic (May 7, 2019)	paternal	clinical testing	Citation Link,
SCV001984825	Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 12, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003925752	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 23, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	paternal	yes	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Hereditary myoclonus-dystonia associated with epilepsy.

Foncke EM, Klein C, Koelman JH, Kramer PL, Schilling K, Müller B, Garrels J, de Carvalho Aguiar P, Liu L, de Froe A, Speelman JD, Ozelius LJ, Tijssen MA.

Neurology. 2003 Jun 24;60(12):1988-90.

PubMed [citation]

PMID:: 12821748

Inherited myoclonus-dystonia and epilepsy: further evidence of an association?

O'Riordan S, Ozelius LJ, de Carvalho Aguiar P, Hutchinson M, King M, Lynch T.

Mov Disord. 2004 Dec;19(12):1456-9.

PubMed [citation]

PMID:: 15389977

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000638422.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

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).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München, SCV001149926.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	paternal	yes	1	blood	not provided		1	not provided	not provided	not provided

From Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego, SCV001984825.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV003925752.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 23, 2024

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