NM_198576.4(AGRN):c.4805C>T (p.Pro1602Leu) 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:: Apr 8, 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:: RCV001317695.8

Allele description

NM_198576.4(AGRN):c.4805C>T (p.Pro1602Leu)

Gene:

AGRN:agrin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.33

Genomic location:

Preferred name:

NM_198576.4(AGRN):c.4805C>T (p.Pro1602Leu)

HGVS:

NC_000001.11:g.1049963C>T
NG_016346.1:g.34841C>T
NM_001305275.2:c.4805C>T
NM_001364727.2:c.4490C>T
NM_198576.3:c.4805C>T
NM_198576.4:c.4805C>TMANE SELECT
NP_001292204.1:p.Pro1602Leu
NP_001351656.1:p.Pro1497Leu
NP_940978.2:p.Pro1602Leu
LRG_198:g.34841C>T
NC_000001.10:g.985343C>T

Protein change:

P1497L

Links:

dbSNP: rs935763466

NCBI 1000 Genomes Browser:

rs935763466

Molecular consequence:

NM_001305275.2:c.4805C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364727.2:c.4490C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198576.4:c.4805C>T - 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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MULTISPECIES: thiaminase II [Staphylococcus]
MULTISPECIES: thiaminase II [Staphylococcus]
gi|446318222|ref|WP_000396077.1|

Protein
PREDICTED: Egretta garzetta exostosin like glycosyltransferase 3 (EXTL3), transc...
PREDICTED: Egretta garzetta exostosin like glycosyltransferase 3 (EXTL3), transcript variant X16, mRNA
gi|1894699849|ref|XM_035895437.1|

Nucleotide
PREDICTED: Egretta garzetta exostosin like glycosyltransferase 3 (EXTL3), transc...
PREDICTED: Egretta garzetta exostosin like glycosyltransferase 3 (EXTL3), transcript variant X11, mRNA
gi|1894699839|ref|XM_035895432.1|

Nucleotide
Homo sapiens cDNA FLJ31924 fis, clone NT2RP7005468
Homo sapiens cDNA FLJ31924 fis, clone NT2RP7005468
gi|16551901|dbj|AK056486.1|

Nucleotide
SRX856384 (1)
SRA

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001508365	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 8, 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

SCV001508365

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 8, 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, SCV001508365.5

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

Description

This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1602 of the AGRN protein (p.Pro1602Leu). 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. This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with AGRN-related conditions. ClinVar contains an entry for this variant (Variation ID: 1018399). 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.

#	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: Aug 11, 2024

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