NM_000263.4(NAGLU):c.1949G>A (p.Gly650Glu) AND multiple conditions

Clinical significance:Pathogenic (Last evaluated: Apr 18, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001036826.2

Allele description [Variation Report for NM_000263.4(NAGLU):c.1949G>A (p.Gly650Glu)]

NM_000263.4(NAGLU):c.1949G>A (p.Gly650Glu)

Gene:
NAGLU:N-acetyl-alpha-glucosaminidase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q21.2
Genomic location:
Preferred name:
NM_000263.4(NAGLU):c.1949G>A (p.Gly650Glu)
HGVS:
  • NC_000017.11:g.42543955G>A
  • NG_011552.1:g.13023G>A
  • NM_000263.4:c.1949G>AMANE SELECT
  • NP_000254.2:p.Gly650Glu
  • NC_000017.10:g.40695973G>A
  • NM_000263.3:c.1949G>A
  • P54802:p.Gly650Glu
Protein change:
G650E
Links:
UniProtKB: P54802#VAR_054736; dbSNP: rs527236037
NCBI 1000 Genomes Browser:
rs527236037
Molecular consequence:
  • NM_000263.4:c.1949G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Mucopolysaccharidosis, MPS-III-B (MPS3B)
Synonyms:
NAGLU DEFICIENCY; Mucopoly-saccharidosis type 3B; Sanfilippo syndrome B; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009656; MedGen: C0086648; OMIM: 252920
Name:
Charcot-Marie-Tooth disease, axonal type 2V (CMT2V)
Synonyms:
CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 2V; CHARCOT-MARIE-TOOTH DISEASE, AXONAL, AUTOSOMAL DOMINANT, TYPE 2V
Identifiers:
MONDO: MONDO:0014665; MedGen: C4225306; Orphanet: 447964; OMIM: 616491

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001200209Invitaecriteria provided, single submitter
Pathogenic
(Apr 18, 2020)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Molecular characterization of 355 mucopolysaccharidosis patients reveals 104 novel mutations.

Pollard LM, Jones JR, Wood TC.

J Inherit Metab Dis. 2013 Mar;36(2):179-87. doi: 10.1007/s10545-012-9533-7. Epub 2012 Sep 14.

PubMed [citation]
PMID:
22976768

Sanfilippo type B syndrome (mucopolysaccharidosis III B): allelic heterogeneity corresponds to the wide spectrum of clinical phenotypes.

Weber B, Guo XH, Kleijer WJ, van de Kamp JJ, Poorthuis BJ, Hopwood JJ.

Eur J Hum Genet. 1999 Jan;7(1):34-44.

PubMed [citation]
PMID:
10094189
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001200209.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces glycine with glutamic acid at codon 650 of the NAGLU protein (p.Gly650Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with mucopolysaccharidosis (PMID: 22976768, 10094189, 23661660). This variant has also been observed to segregate with mucopolysaccharidosis type IIIB in a family (PMID: 23661660). ClinVar contains an entry for this variant (Variation ID: 143188). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Nov 27, 2021

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