NM_000263.4(NAGLU):c.1694G>T (p.Arg565Leu) AND multiple conditions

Clinical significance:Pathogenic (Last evaluated: Feb 19, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001070181.2

Allele description [Variation Report for NM_000263.4(NAGLU):c.1694G>T (p.Arg565Leu)]

NM_000263.4(NAGLU):c.1694G>T (p.Arg565Leu)

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.1694G>T (p.Arg565Leu)
HGVS:
  • NC_000017.11:g.42543700G>T
  • NG_011552.1:g.12768G>T
  • NM_000263.4:c.1694G>TMANE SELECT
  • NP_000254.2:p.Arg565Leu
  • NC_000017.10:g.40695718G>T
  • NM_000263.3:c.1694G>T
Protein change:
R565L
Links:
dbSNP: rs104894598
NCBI 1000 Genomes Browser:
rs104894598
Molecular consequence:
  • NM_000263.4:c.1694G>T - 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

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)
OriginMethodCitations
SCV001235397Invitaecriteria provided, single submitter
Pathogenic
(Feb 19, 2019)
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

Prevalence and Novel Mutations of Lysosomal Storage Disorders in United Arab Emirates : LSD in UAE.

Al-Jasmi FA, Tawfig N, Berniah A, Ali BR, Taleb M, Hertecant JL, Bastaki F, Souid AK.

JIMD Rep. 2013;10:1-9. doi: 10.1007/8904_2012_182. Epub 2013 Jan 1.

PubMed [citation]
PMID:
23430803
PMCID:
PMC3755583

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, SCV001235397.2

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

Description

This sequence change replaces arginine with leucine at codon 565 of the NAGLU protein (p.Arg565Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is present in population databases (rs104894598, ExAC 0.006%). This variant has been observed to segregate with mucopolysaccharidosis type III in families (PMID: 23430803). ClinVar contains an entry for this variant (Variation ID: 557013). 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). This variant disrupts the p.Arg565 amino acid residue in NAGLU. Other variant(s) that disrupt this residue have been observed in individuals with NAGLU-related conditions (PMID: 10094189, 15933803), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. 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

Support Center