NM_000263.4(NAGLU):c.1834A>G (p.Ser612Gly) AND multiple conditions

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 15, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000686454.11

Allele description [Variation Report for NM_000263.4(NAGLU):c.1834A>G (p.Ser612Gly)]

NM_000263.4(NAGLU):c.1834A>G (p.Ser612Gly)

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.1834A>G (p.Ser612Gly)

HGVS:

NC_000017.11:g.42543840A>G
NG_011552.1:g.12908A>G
NM_000263.4:c.1834A>GMANE SELECT
NP_000254.2:p.Ser612Gly
NC_000017.10:g.40695858A>G
NM_000263.3:c.1834A>G
p.S612G

Protein change:

S612G

Links:

dbSNP: rs148881970

NCBI 1000 Genomes Browser:

rs148881970

Molecular consequence:

NM_000263.4:c.1834A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Mucopolysaccharidosis, MPS-III-B (MPS3B)
Synonyms:: N-ACETYL-ALPHA-D-GLUCOSAMINIDASE DEFICIENCY; NAGLU DEFICIENCY; 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
SCV000813973	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 15, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 9443875, 20852935, 25256447, 26907177, 21712855, 28492532
SCV000894120	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 15, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000813973

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 15, 2024)

germline

clinical testing

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

SCV000894120

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 15, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Genotype-phenotype correspondence in Sanfilippo syndrome type B.

Zhao HG, Aronovich EL, Whitley CB.

Am J Hum Genet. 1998 Jan;62(1):53-63.

PubMed [citation]

PMID:: 9443875
PMCID:: PMC1376807

Mucopolysaccharidosis type IIIB may predominantly present with an attenuated clinical phenotype.

Valstar MJ, Bruggenwirth HT, Olmer R, Wevers RA, Verheijen FW, Poorthuis BJ, Halley DJ, Wijburg FA.

J Inherit Metab Dis. 2010 Dec;33(6):759-67. doi: 10.1007/s10545-010-9199-y. Epub 2010 Sep 18.

PubMed [citation]

PMID:: 20852935
PMCID:: PMC2992652

See all PubMed Citations (7)

PMC

Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL.

Genetics in medicine : official journal of the American College of Medical Genetics. 2015 Mar 5; 17(5): 405-424

PMC [article]

PMCID:: PMC4544753
PMID:: 25741868
DOI:: 10.1038/gim.2015.30

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000813973.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 612 of the NAGLU protein (p.Ser612Gly). This variant is present in population databases (rs148881970, gnomAD 0.01%). This missense change has been observed in individual(s) with a mild form of mucopolysaccharidosis type IIIB (PMID: 9443875, 20852935, 21712855, 25256447, 26907177). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 522823). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NAGLU protein function. Experimental studies have shown that this missense change affects NAGLU function (PMID: 21712855). 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

From Fulgent Genetics, Fulgent Genetics, SCV000894120.3

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

#	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 6, 2025

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