NM_000434.4(NEU1):c.679G>A (p.Gly227Arg) AND not provided

Clinical significance:Pathogenic (Last evaluated: Feb 1, 2021)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000494284.8

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]
Observations:
2

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000583127GeneDxcriteria provided, single submitter
Pathogenic
(Sep 13, 2019)
germlineclinical testing

Citation Link,

SCV001421404Invitaecriteria provided, single submitter
Pathogenic
(Oct 16, 2019)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

SCV001502480CeGaT Praxis fuer Humangenetik Tuebingencriteria provided, single submitter
Pathogenic
(Feb 1, 2021)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes2not providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Type II sialidosis: review of the clinical spectrum and identification of a new splicing defect with chitotriosidase assessment in two patients.

Caciotti A, Di Rocco M, Filocamo M, Grossi S, Traverso F, d'Azzo A, Cavicchi C, Messeri A, Guerrini R, Zammarchi E, Donati MA, Morrone A.

J Neurol. 2009 Nov;256(11):1911-5. doi: 10.1007/s00415-009-5213-4. Epub 2009 Jul 1. Review.

PubMed [citation]
PMID:
19568825

Type 1 sialidosis presenting with ataxia, seizures and myoclonus with no visual involvement.

Mohammad AN, Bruno KA, Hines S, Atwal PS.

Mol Genet Metab Rep. 2018 Jun;15:11-14. doi: 10.1016/j.ymgmr.2017.12.005.

PubMed [citation]
PMID:
30023283
PMCID:
PMC6047061
See all PubMed Citations (6)

Details of each submission

From GeneDx, SCV000583127.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 31956508, 10767332, 24808020, 26141460, 25401298, 19568825, 30023283, 11063730, 33144682)

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

From Invitae, SCV001421404.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change replaces glycine with arginine at codon 227 of the NEU1 protein (p.Gly227Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs769765227, ExAC 0.009%). This variant has been observed in the homozygous state or in combination with another NEU1 variant in individuals with sialidosis and has been observed to segregate with sialidosis in families (PMID: 10767332, 19568825, 30023283, 24808020, 26141460). ClinVar contains an entry for this variant (Variation ID: 430342). This variant has been reported to affect NEU1 protein function (PMID: 10767332). For these reasons, this variant has been classified as Pathogenic.

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

From CeGaT Praxis fuer Humangenetik Tuebingen, SCV001502480.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided2not providednot providednot provided

Last Updated: Oct 6, 2021

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