NM_000117.3(EMD):c.650_654dup (p.Gln219fs) AND X-linked Emery-Dreifuss muscular dystrophy

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

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Apr 18, 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:: RCV001850141.7

Allele description

NM_000117.3(EMD):c.650_654dup (p.Gln219fs)

Gene:

EMD:emerin [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

Xq28

Genomic location:

Preferred name:

NM_000117.3(EMD):c.650_654dup (p.Gln219fs)

Other names:

p.Gln219TrpfsX20

HGVS:

NC_000023.10:g.153609432_153609433insGGGCT
NC_000023.11:g.154381077TGGGC[3]
NG_008677.1:g.11642TGGGC[3]
NM_000117.3:c.650_654dupMANE SELECT
NP_000108.1:p.Gln219fs
LRG_745:g.11642TGGGC[3]
NC_000023.10:g.153609432_153609433insGGGCT
NC_000023.10:g.153609437TGGGC[3]
NC_000023.10:g.153609446_153609447insTGGGC
NM_000117.2:c.650_654dupTGGGC

Protein change:

Q219fs

Links:

dbSNP: rs730880352

NCBI 1000 Genomes Browser:

rs730880352

Molecular consequence:

NM_000117.3:c.650_654dup - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: X-linked Emery-Dreifuss muscular dystrophy
Synonyms:: Muscular dystrophy, tardive Emery-Dreifuss type, with contractures
Identifiers:: MONDO: MONDO:0010680; MedGen: C0751337; Orphanet: 261; Orphanet: 98863

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002234004	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 18, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 8595406, 17355552, 18646565, 31474437, 28492532
SCV002580839	MGZ Medical Genetics Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Feb 15, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002766777	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 31, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 8595406, 17355552, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002234004

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 18, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV002580839

MGZ Medical Genetics Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Feb 15, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002766777

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 31, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Emerinopathy and laminopathy clinical, pathological and molecular features of muscular dystrophy with nuclear envelopathy in Japan.

Astejada MN, Goto K, Nagano A, Ura S, Noguchi S, Nonaka I, Nishino I, Hayashi YK.

Acta Myol. 2007 Dec;26(3):159-64. Review.

PubMed [citation]

PMID:: 18646565
PMCID:: PMC2949309

X-linked Emery-Dreifuss muscular dystrophy manifesting with adult onset axial weakness, camptocormia, and minimal joint contractures.

Brisset M, Ben Yaou R, Carlier RY, Chanut A, Nicolas G, Romero NB, Wahbi K, Decrocq C, Leturcq F, Laforêt P, Malfatti E.

Neuromuscul Disord. 2019 Sep;29(9):678-683. doi: 10.1016/j.nmd.2019.06.009. Epub 2019 Jun 19.

PubMed [citation]

PMID:: 31474437

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV002234004.3

#	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: 179133). This variant is also known as 1712_1713ins TGGGC. This premature translational stop signal has been observed in individual(s) with Emery-Dreifuss muscular dystrophy (PMID: 8595406, 17355552, 18646565, 31474437). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln219Trpfs*20) in the EMD gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 36 amino acid(s) of the EMD protein.

#	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 MGZ Medical Genetics Center, SCV002580839.1

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

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002766777.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Emery-Dreifuss muscular dystrophy 1 (MIM#310300). (I) 0109 - This gene is associated with X-linked recessive disease. (I) 0205 - Variant is predicted to result in a truncated protein (premature termination codon is NOT located at least 54 nucleotides upstream of the final exon-exon junction with less than 1/3 of the protein sequence affected. (SP) 0253 - This variant is hemizygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0702 - Other truncation variants comparable to the one identified in this case have strong previous evidence for pathogenicity (ClinVar). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported in individuals with Emery-Dreifuss muscular dystrophy (PMID: 8595406, 17355552). A different c. change which results in the same p. change (c.640_644dup; p.Q219Wfs*20) has also been reported as likely pathogenic and pathogenic (ClinVar). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

#	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

Last Updated: May 7, 2024

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