NM_000080.4(CHRNE):c.971del (p.Ile324fs) AND Congenital myasthenic syndrome 4A

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 20, 2024
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:: RCV000641735.12

Allele description [Variation Report for NM_000080.4(CHRNE):c.971del (p.Ile324fs)]

NM_000080.4(CHRNE):c.971del (p.Ile324fs)

Gene:

CHRNE:cholinergic receptor nicotinic epsilon subunit [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

17p13.2

Genomic location:

Preferred name:

NM_000080.4(CHRNE):c.971del (p.Ile324fs)

HGVS:

NC_000017.11:g.4899529del
NG_008029.2:g.8547del
NG_028005.1:g.71190del
NM_000080.4:c.971delMANE SELECT
NP_000071.1:p.Ile324fs
LRG_1254t1:c.971del
LRG_1254:g.8547del
LRG_1254p1:p.Ile324fs
NC_000017.10:g.4802824del
NM_000080.3:c.971del
NM_000080.3:c.971delT
NM_000080.4:c.971delTMANE SELECT

Protein change:

I324fs

Links:

OMIM: 100725.0006; dbSNP: rs879255562

NCBI 1000 Genomes Browser:

rs879255562

Molecular consequence:

NM_000080.4:c.971del - 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
SCV000763383	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 31, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 22678886, 11030414, 16087917, 28492532
SCV004212569	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 20, 2024)	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

SCV000763383

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 31, 2024)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV004212569

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 20, 2024)

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

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

Immature end-plates and utrophin deficiency in congenital myasthenic syndrome caused by epsilon-AChR subunit truncating mutations.

Sieb JP, Kraner S, Rauch M, Steinlein OK.

Hum Genet. 2000 Aug;107(2):160-4.

PubMed [citation]

PMID:: 11030414

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000763383.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Ile324Thrfs*61) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with autosomal recessive congenital myasthenic syndromes (PMID: 11030414, 16087917). This variant is also known as 911delT. ClinVar contains an entry for this variant (Variation ID: 18348). For these reasons, this variant has been classified as Pathogenic.

#	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, SCV004212569.2

#	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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