NM_000080.4(CHRNE):c.1062_1081dup (p.Glu361fs) AND Congenital myasthenic syndrome 4A

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Apr 30, 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:: RCV001960611.5

Allele description [Variation Report for NM_000080.4(CHRNE):c.1062_1081dup (p.Glu361fs)]

NM_000080.4(CHRNE):c.1062_1081dup (p.Glu361fs)

Genes:

LOC130060041:ATAC-STARR-seq lymphoblastoid silent region 8050 [Gene]
CHRNE:cholinergic receptor nicotinic epsilon subunit [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

17p13.2

Genomic location:

Preferred name:

NM_000080.4(CHRNE):c.1062_1081dup (p.Glu361fs)

HGVS:

NC_000017.11:g.4899336_4899355dup
NG_008029.2:g.8721_8740dup
NG_028005.1:g.70997_71016dup
NM_000080.4:c.1062_1081dupMANE SELECT
NP_000071.1:p.Glu361fs
LRG_1254t1:c.1062_1081dup
LRG_1254:g.8721_8740dup
LRG_1254p1:p.Glu361fs
NC_000017.10:g.4802630_4802631insCGGGCGGCGGCGGGGAGCCC
NC_000017.10:g.4802631_4802650dup

Protein change:

E361fs

Links:

dbSNP: rs2151094729

NCBI 1000 Genomes Browser:

rs2151094729

Molecular consequence:

NM_000080.4:c.1062_1081dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Congenital myasthenic syndrome 4A
Synonyms:: CONGENITAL MYASTHENIC SYNDROME TYPE Ia1; Myasthenic syndrome, congenital, 4a, slow-channel; MYASTHENIC SYNDROME, CONGENITAL, 4A, SLOW-CHANNEL, AUTOSOMAL RECESSIVE
Identifiers:: MONDO: MONDO:0011600; MedGen: C4225413; Orphanet: 590; OMIM: 605809

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002231174	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 14, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 14532324, 22678886, 28492532
SCV004214260	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 30, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002231174

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 14, 2022)

germline

clinical testing

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

SCV004214260

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 30, 2023)

unknown

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A frameshifting mutation in CHRNE unmasks skipping of the preceding exon.

Ohno K, Milone M, Shen XM, Engel AG.

Hum Mol Genet. 2003 Dec 1;12(23):3055-66. Epub 2003 Oct 7.

PubMed [citation]

PMID:: 14532324

Congenital myasthenic syndromes: achievements and limitations of phenotype-guided gene-after-gene sequencing in diagnostic practice: a study of 680 patients.

Abicht A, Dusl M, Gallenmüller C, Guergueltcheva V, Schara U, Della Marina A, Wibbeler E, Almaras S, Mihaylova V, von der Hagen M, Huebner A, Chaouch A, Müller JS, Lochmüller H.

Hum Mutat. 2012 Oct;33(10):1474-84. doi: 10.1002/humu.22130. Epub 2012 Jun 27.

PubMed [citation]

PMID:: 22678886

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002231174.3

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant is also known as c.1021ins20. This premature translational stop signal has been observed in individual(s) with clinical features of congenital myasthenic syndrome (PMID: 14532324). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu361Glyfs*31) in the CHRNE gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CHRNE are known to be pathogenic (PMID: 22678886).

#	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 Baylor Genetics, SCV004214260.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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