NM_198576.4(AGRN):c.3724C>T (p.Gln1242Ter) AND Congenital myasthenic syndrome 8

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 10, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001382085.5

Allele description [Variation Report for NM_198576.4(AGRN):c.3724C>T (p.Gln1242Ter)]

NM_198576.4(AGRN):c.3724C>T (p.Gln1242Ter)

Gene:

AGRN:agrin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.33

Genomic location:

Preferred name:

NM_198576.4(AGRN):c.3724C>T (p.Gln1242Ter)

HGVS:

NC_000001.11:g.1047868C>T
NG_016346.1:g.32746C>T
NM_001305275.2:c.3724C>T
NM_001364727.2:c.3409C>T
NM_198576.4:c.3724C>TMANE SELECT
NP_001292204.1:p.Gln1242Ter
NP_001351656.1:p.Gln1137Ter
NP_940978.2:p.Gln1242Ter
LRG_198:g.32746C>T
NC_000001.10:g.983248C>T

Protein change:

Q1137*

Links:

dbSNP: rs2100666336

NCBI 1000 Genomes Browser:

rs2100666336

Molecular consequence:

NM_001305275.2:c.3724C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001364727.2:c.3409C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_198576.4:c.3724C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Congenital myasthenic syndrome 8
Synonyms:: MYASTHENIC SYNDROME, CONGENITAL, DUE TO AGRIN DEFICIENCY; Myasthenic syndrome, congenital, 8, with pre- and postsynaptic defects
Identifiers:: MONDO: MONDO:0014052; MedGen: C3808739; Orphanet: 590; OMIM: 615120

Recent activity

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Schizosaccharomyces pombe DNA-binding transcription factor Hsf1 (hsf1), mRNA
Schizosaccharomyces pombe DNA-binding transcription factor Hsf1 (hsf1), mRNA
gi|2745690520|ref|NM_001020275.3|

Nucleotide
LOC130060204 [Homo sapiens]
LOC130060204 [Homo sapiens]
Gene ID:130060204

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001580715	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 10, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24951643, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001580715

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 10, 2022)

germline

clinical testing

PubMed (2)
[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

Citations

PubMed

Agrin mutations lead to a congenital myasthenic syndrome with distal muscle weakness and atrophy.

Nicole S, Chaouch A, Torbergsen T, Bauché S, de Bruyckere E, Fontenille MJ, Horn MA, van Ghelue M, Løseth S, Issop Y, Cox D, Müller JS, Evangelista T, Stålberg E, Ioos C, Barois A, Brochier G, Sternberg D, Fournier E, Hantaï D, Abicht A, Dusl M, et al.

Brain. 2014 Sep;137(Pt 9):2429-43. doi: 10.1093/brain/awu160. Epub 2014 Jun 20.

PubMed [citation]

PMID:: 24951643

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001580715.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1070058). This variant has not been reported in the literature in individuals affected with AGRN-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln1242*) in the AGRN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AGRN are known to be pathogenic (PMID: 24951643).

#	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: Sep 29, 2024

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