NM_000434.4(NEU1):c.679G>A (p.Gly227Arg) AND Sialidosis

Clinical significance:Pathogenic (Last evaluated: Mar 21, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000587143.1

Allele description [Variation Report for NM_000434.4(NEU1):c.679G>A (p.Gly227Arg)]

NM_000434.4(NEU1):c.679G>A (p.Gly227Arg)

Gene:
NEU1:neuraminidase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6p21.33
Genomic location:
Preferred name:
NM_000434.4(NEU1):c.679G>A (p.Gly227Arg)
HGVS:
  • NC_000006.12:g.31860558C>T
  • NG_008201.1:g.7375G>A
  • NM_000434.4:c.679G>AMANE SELECT
  • NP_000425.1:p.Gly227Arg
  • NC_000006.11:g.31828335C>T
  • NM_000434.3:c.679G>A
Protein change:
G227R
Links:
dbSNP: rs769765227
NCBI 1000 Genomes Browser:
rs769765227
Molecular consequence:
  • NM_000434.4:c.679G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Sialidosis
Identifiers:
MONDO: MONDO:0017734; MedGen: C0268226; Orphanet: 309294

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000696697Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Mar 21, 2016)
germlineclinical testing

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

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

Summary from all submissions

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

Citations

PubMed

Expanding sialidosis spectrum by genome-wide screening: NEU1 mutations in adult-onset myoclonus.

Canafoglia L, Robbiano A, Pareyson D, Panzica F, Nanetti L, Giovagnoli AR, Venerando A, Gellera C, Franceschetti S, Zara F.

Neurology. 2014 Jun 3;82(22):2003-6. doi: 10.1212/WNL.0000000000000482. Epub 2014 May 7. Review.

PubMed [citation]
PMID:
24808020

Characterization of the sialidase molecular defects in sialidosis patients suggests the structural organization of the lysosomal multienzyme complex.

Lukong KE, Elsliger MA, Chang Y, Richard C, Thomas G, Carey W, Tylki-Szymanska A, Czartoryska B, Buchholz T, Criado GR, Palmeri S, Pshezhetsky AV.

Hum Mol Genet. 2000 Apr 12;9(7):1075-85.

PubMed [citation]
PMID:
10767332

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000696697.1

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

Description

Variant summary: The NEU1 c.679G>A variant affects a conserved nucleotide, resulting in amino acid change from Gly to Arg. 4/4 in-silico tools predict damaging outcome for this variant (SNPs&GO not captured due to low reliability index). Functional studies show that G227R has a sialidase activity of <10% of normal, and lacks normal processing and lysosomal targeting (Lukong_Hum. Mol. Genet._2000). This variant was found in 5/120902 control chromosomes at a frequency of 0.0000414, which does not significantly exceed maximal expected frequency of a pathogenic NEU1 allele (0.001118). The variant has been identified in homozygous state in patients with Sialidosis type II and in compound heterozygous state in patients with progressive myoclonus epilepsies or late-onset action myoclonus. Taken together, this variant was classified as pathogenic.

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

Last Updated: Oct 6, 2021

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