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

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 4, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001036826.6

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
Synonyms:: CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 2V; CHARCOT-MARIE-TOOTH DISEASE, AXONAL, AUTOSOMAL DOMINANT, TYPE 2V
Identifiers:: MONDO: MONDO:0014665; MedGen: C5569050; Orphanet: 447964; OMIM: 616491

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001200209	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 4, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 10094189, 22976768, 23661660, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001200209

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 4, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

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

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001200209.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 650 of the NAGLU protein (p.Gly650Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with mucopolysaccharidosis (PMID: 10094189, 22976768, 23661660). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 143188). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NAGLU protein function. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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