NM_198576.4(AGRN):c.4786C>T (p.Pro1596Ser) AND Congenital myasthenic syndrome 8

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 29, 2018
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:: RCV000651358.8

Allele description [Variation Report for NM_198576.4(AGRN):c.4786C>T (p.Pro1596Ser)]

NM_198576.4(AGRN):c.4786C>T (p.Pro1596Ser)

Gene:

AGRN:agrin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.33

Genomic location:

Preferred name:

NM_198576.4(AGRN):c.4786C>T (p.Pro1596Ser)

HGVS:

NC_000001.11:g.1049944C>T
NG_016346.1:g.34822C>T
NM_001305275.2:c.4786C>T
NM_001364727.2:c.4471C>T
NM_198576.4:c.4786C>TMANE SELECT
NP_001292204.1:p.Pro1596Ser
NP_001351656.1:p.Pro1491Ser
NP_940978.2:p.Pro1596Ser
LRG_198:g.34822C>T
NC_000001.10:g.985324C>T
NM_198576.3:c.4786C>T

Protein change:

P1491S

Links:

dbSNP: rs777910926

NCBI 1000 Genomes Browser:

rs777910926

Molecular consequence:

NM_001305275.2:c.4786C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364727.2:c.4471C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198576.4:c.4786C>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000773209	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 29, 2018)	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

SCV000773209

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 29, 2018)

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000773209.5

#	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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with AGRN-related disease. This variant is present in population databases (rs777910926, ExAC 0.003%). This sequence change replaces proline with serine at codon 1596 of the AGRN protein (p.Pro1596Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine.

#	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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