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NM_198576.4(AGRN):c.226G>A (p.Gly76Ser) AND Congenital myasthenic syndrome 8

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Sep 9, 2020
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:
RCV001377978.15

Allele description [Variation Report for NM_198576.4(AGRN):c.226G>A (p.Gly76Ser)]

NM_198576.4(AGRN):c.226G>A (p.Gly76Ser)

Genes:
LOC126805576:P300/CBP strongly-dependent group 1 enhancer GRCh37_chr1:956772-957971 [Gene]
AGRN:agrin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p36.33
Genomic location:
Preferred name:
NM_198576.4(AGRN):c.226G>A (p.Gly76Ser)
HGVS:
  • NC_000001.11:g.1022225G>A
  • NG_016346.1:g.7103G>A
  • NM_001305275.2:c.226G>A
  • NM_198576.4:c.226G>AMANE SELECT
  • NP_001292204.1:p.Gly76Ser
  • NP_940978.2:p.Gly76Ser
  • LRG_198:g.7103G>A
  • NC_000001.10:g.957605G>A
  • NM_198576.3:c.226G>A
Protein change:
G76S
Links:
dbSNP: rs756623659
NCBI 1000 Genomes Browser:
rs756623659
Molecular consequence:
  • NM_001305275.2:c.226G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198576.4:c.226G>A - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001575441Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Sep 9, 2020) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Nothing to display

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001575441.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces glycine with serine at codon 76 of the AGRN protein (p.Gly76Ser). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs756623659, ExAC 0.002%). This variant has been observed in individual(s) with congenital myasthenic syndrome (PMID: 24951643). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 243036). Experimental studies have shown that this variant affects AGRN protein function (PMID: 24951643). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 18, 2024