NM_000434.4(NEU1):c.544A>G (p.Ser182Gly) AND Sialidosis

Clinical significance:Pathogenic (Last evaluated: Sep 26, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_000434.4(NEU1):c.544A>G (p.Ser182Gly)]

NM_000434.4(NEU1):c.544A>G (p.Ser182Gly)

NEU1:neuraminidase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000434.4(NEU1):c.544A>G (p.Ser182Gly)
  • NC_000006.12:g.31861259T>C
  • NG_008201.1:g.6674A>G
  • NG_023058.1:g.22788A>G
  • NM_000434.4:c.544A>GMANE SELECT
  • NP_000425.1:p.Ser182Gly
  • NC_000006.11:g.31829036T>C
  • NM_000434.3:c.544A>G
Protein change:
dbSNP: rs398123392
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000434.4:c.544A>G - missense variant - [Sequence Ontology: SO:0001583]


MONDO: MONDO:0017734; MedGen: C0268226; Orphanet: 309294

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000919869Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
(Sep 26, 2018)
germlineclinical testing

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

Citation Link

Summary from all submissions

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



First report of two Taiwanese siblings with sialidosis type I: a 10-year follow-up study.

Chen CM, Lai SC, Chen IC, Hsu KC, Lyu RK, Ro LS, Chang HS.

J Neurol Sci. 2006 Aug 15;247(1):65-9. Epub 2006 May 18.

PubMed [citation]

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]

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000919869.1

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


Variant summary: NEU1 c.544A>G (p.Ser182Gly) results in a non-conservative amino acid change located in the Sialidase domain of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 9.5e-05 in 241352 control chromosomes (gnomAD and publications). This frequency is not significantly higher than expected for a pathogenic variant in NEU1 causing Sialidosis (9.5e-05 vs 0.0011), allowing no conclusion about variant significance. c.544A>G has been reported in the literature in multiple individuals affected with Sialidosis (Chen_2006, Lukong_2000). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function (Chen_2006, Lukong_2000). The most pronounced variant effect results in <10% of normal activity. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Jun 14, 2021

Support Center