NM_198576.4(AGRN):c.1951C>G (p.Leu651Val) AND Congenital myasthenic syndrome 8

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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 4, 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:: RCV001064148.7

Allele description

NM_198576.4(AGRN):c.1951C>G (p.Leu651Val)

Gene:

AGRN:agrin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.33

Genomic location:

Preferred name:

NM_198576.4(AGRN):c.1951C>G (p.Leu651Val)

HGVS:

NC_000001.11:g.1043975C>G
NG_016346.1:g.28853C>G
NM_001305275.2:c.1951C>G
NM_001364727.2:c.1636C>G
NM_198576.4:c.1951C>GMANE SELECT
NP_001292204.1:p.Leu651Val
NP_001351656.1:p.Leu546Val
NP_940978.2:p.Leu651Val
LRG_198:g.28853C>G
NC_000001.10:g.979355C>G
NM_198576.3:c.1951C>G

Protein change:

L546V

Links:

dbSNP: rs754639566

NCBI 1000 Genomes Browser:

rs754639566

Molecular consequence:

NM_001305275.2:c.1951C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001364727.2:c.1636C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_198576.4:c.1951C>G - missense variant - [Sequence Ontology: SO:0001583]

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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ad47a06.s1 Stratagene lung carcinoma 937218 Homo sapiens cDNA clone IMAGE:884818...
ad47a06.s1 Stratagene lung carcinoma 937218 Homo sapiens cDNA clone IMAGE:884818 3', mRNA sequence
gi|2630839|gnl|dbEST|1374924|gb|AA6 .1|

Nucleotide
Homo sapiens signal induced proliferation associated 1 like 1 (SIPA1L1), transcr...
Homo sapiens signal induced proliferation associated 1 like 1 (SIPA1L1), transcript variant 8, mRNA
gi|1677530128|ref|NM_001354288.2|

Nucleotide
Homo sapiens high-risk human papilloma viruses E6 oncoproteins targeted protein ...
Homo sapiens high-risk human papilloma viruses E6 oncoproteins targeted protein E6TP1 alpha mRNA, complete cds
gi|4151327|gb|AF090989.1|

Nucleotide
Homo sapiens cytochrome P450 family 2 subfamily E member 1 (CYP2E1), mRNA
Homo sapiens cytochrome P450 family 2 subfamily E member 1 (CYP2E1), mRNA
gi|1519313150|ref|NM_000773.4|

Nucleotide
Cercideae LEGCYC2 (LEGCYC2) gene, partial cds.
Cercideae LEGCYC2 (LEGCYC2) gene, partial cds.
PopSet: 992215609

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001229030	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 4, 2022)	germline	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

SCV001229030

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 4, 2022)

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

Citations

PubMed

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 Invitae, SCV001229030.5

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 858300). This variant has not been reported in the literature in individuals affected with AGRN-related conditions. This variant is present in population databases (rs754639566, gnomAD 0.01%). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 651 of the AGRN protein (p.Leu651Val).

#	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: Feb 14, 2024

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