The NAGLU c.1834A>G (p.Ser612Gly) variant has been reported in four studies and in a total of 11 probands with mucopolysaccharidosis including ten probands in a compound heterozygous state and one proband in a homozygous state (Zhao et al. 1998; Verhoeven et al. 2010; Valstar et al. 2010; Selmer et al. 2012). Segregation analysis confirmed co-segregation with disease in a clear autosomal recessive inheritance pattern in two families (Zhao et al. 1998; Selmer et al. 2012). Control data are unavailable for this variant, which is reported at a frequency of 0.00022 in the European (non-Finnish) population of the Exome Aggregation Consortium. Two studies demonstrated deficient alpha-N-acetyl glucosaminidase (NAGLU) enzyme activity in cultured fibroblasts from affected subjects (Verhoeven et al. 2010; Selmer et al. 2012). In five of the six families reported, this variant was associated with an attenuated phenotype of MPS IIIB with a slower progression of disease. Based on the collective evidence the p.Ser612Gly variant is classified as a pathogenic variant for mucopolysaccharidosis type III. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
ClinVar Genomic variation as it relates to human health
NM_000263.4(NAGLU):c.1834A>G (p.Ser612Gly)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(12)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Pathogenic
12
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000263.4(NAGLU):c.1834A>G (p.Ser612Gly)
Variation ID: 522823 Accession: VCV000522823.24
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 17q21.2 17: 42543840 (GRCh38) [ NCBI UCSC ] 17: 40695858 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 29, 2018 Nov 17, 2024 Apr 22, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000263.4:c.1834A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000254.2:p.Ser612Gly missense NC_000017.11:g.42543840A>G NC_000017.10:g.40695858A>G NG_011552.1:g.12908A>G - Protein change
- S612G
- Other names
- -
- Canonical SPDI
- NC_000017.11:42543839:A:G
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
0.00020 (G)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Trans-Omics for Precision Medicine (TOPMed) 0.00012
The Genome Aggregation Database (gnomAD) 0.00013
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015
1000 Genomes Project 0.00020
1000 Genomes Project 30x 0.00031
The Genome Aggregation Database (gnomAD), exomes 0.00005
Exome Aggregation Consortium (ExAC) 0.00012
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| NAGLU | - | - |
GRCh38 GRCh37 |
1055 | 1276 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
|
Apr 22, 2024 | RCV000625994.10 | |
| not provided (1) |
no classification provided
|
- | RCV001030809.2 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Jan 29, 2024 | RCV000686454.9 | |
| Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Apr 21, 2023 | RCV001268050.8 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Feb 09, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Mucopolysaccharidosis, MPS-III-B
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
paternal
|
Undiagnosed Diseases Network, NIH
Study: Undiagnosed Diseases Network (NIH), UDN
Accession: SCV000746600.1 First in ClinVar: Apr 29, 2018 Last updated: Apr 29, 2018 |
Number of individuals with the variant: 1
Clinical Features:
Urinary incontinence (present) , Thick vermilion border (present) , Sleep disturbance (present) , Rod-cone dystrophy (present) , Repetitive compulsive behavior (present) , Prominent supraorbital ridges … (more)
Urinary incontinence (present) , Thick vermilion border (present) , Sleep disturbance (present) , Rod-cone dystrophy (present) , Repetitive compulsive behavior (present) , Prominent supraorbital ridges (present) , Mental deterioration (present) , Memory impairment (present) , Macrotia (present) , Hypersexuality (present) , Hyperactivity (present) , Gait imbalance (present) , Forceps delivery (present) , Developmental regression (present) , Dementia (present) , Chronic diarrhea (present) , Brain atrophy (present) , Bowel incontinence (present) , Coxa plana (present) , Autistic disorder of childhood onset (present) , Abnormal aggressive, impulsive or violent behavior (present) (less)
Age: 20-29 years
Sex: male
Ethnicity/Population group: White
Testing laboratory: Baylor Genetics
Date variant was reported to submitter: 2017-02-09
Testing laboratory interpretation: Pathogenic
|
|
|
Pathogenic
(Nov 01, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Mucopolysaccharidosis, MPS-III-B
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000914767.1
First in ClinVar: May 27, 2019 Last updated: May 27, 2019 |
Comment:
The NAGLU c.1834A>G (p.Ser612Gly) variant has been reported in four studies and in a total of 11 probands with mucopolysaccharidosis including ten probands in a … (more)
The NAGLU c.1834A>G (p.Ser612Gly) variant has been reported in four studies and in a total of 11 probands with mucopolysaccharidosis including ten probands in a compound heterozygous state and one proband in a homozygous state (Zhao et al. 1998; Verhoeven et al. 2010; Valstar et al. 2010; Selmer et al. 2012). Segregation analysis confirmed co-segregation with disease in a clear autosomal recessive inheritance pattern in two families (Zhao et al. 1998; Selmer et al. 2012). Control data are unavailable for this variant, which is reported at a frequency of 0.00022 in the European (non-Finnish) population of the Exome Aggregation Consortium. Two studies demonstrated deficient alpha-N-acetyl glucosaminidase (NAGLU) enzyme activity in cultured fibroblasts from affected subjects (Verhoeven et al. 2010; Selmer et al. 2012). In five of the six families reported, this variant was associated with an attenuated phenotype of MPS IIIB with a slower progression of disease. Based on the collective evidence the p.Ser612Gly variant is classified as a pathogenic variant for mucopolysaccharidosis type III. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
|
|
|
Pathogenic
(Oct 23, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
(Unknown mechanism)
Affected status: yes
Allele origin:
germline
|
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001446654.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Global developmental delay (present) , Aphasia (present)
Sex: female
|
|
|
Pathogenic
(Dec 13, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Knight Diagnostic Laboratories, Oregon Health and Sciences University
Accession: SCV001448901.1
First in ClinVar: Dec 11, 2020 Last updated: Dec 11, 2020 |
Number of individuals with the variant: 1
Clinical Features:
Sacral dimple (present) , Tethered cord (present) , Arnold-Chiari type I malformation (present) , Syringomyelia (present) , Short palpebral fissure (present) , Myopia (disease) (present) … (more)
Sacral dimple (present) , Tethered cord (present) , Arnold-Chiari type I malformation (present) , Syringomyelia (present) , Short palpebral fissure (present) , Myopia (disease) (present) , Hypermetropia (present) , Abnormality of dental structure (present) , Agenesis of maxillary incisor (present) , Hemangioma (present) , Hip dysplasia (present) , Joint hypermobility (present) , Rectal prolapse (present) , Renal malrotation (present) , Atrial septal defect (present) , Ventricular septal defect (present) , Bicuspid aortic valve (present) , Patent ductus arteriosus (present) , Premature thelarche (present) , Generalized hypotonia (present) , Expressive language delay (present) , Bilateral cleft lip and palate (present) , Microcephaly (present) , Conductive hearing impairment (present) , Broad nasal tip (present) , Low-set ears (present) , Full cheeks (present) , Anteverted ears (present) (less)
Sex: female
|
|
|
Pathogenic
(Oct 07, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Mucopolysaccharidosis, MPS-III-B
Charcot-Marie-Tooth disease axonal type 2V
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV000894120.2
First in ClinVar: Mar 31, 2019 Last updated: Dec 31, 2022 |
|
|
|
Pathogenic
(Apr 21, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV004168103.1
First in ClinVar: Nov 25, 2023 Last updated: Nov 25, 2023 |
Comment:
Published functional studies demonstrate a damaging effect, as the variant results in loss of enzyme activity (Clark et al., 2018); Not observed at significant frequency … (more)
Published functional studies demonstrate a damaging effect, as the variant results in loss of enzyme activity (Clark et al., 2018); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29979746, 28751108, 20852935, 9443875, 35848209, 31718697, 34347683, 25256447, 21712855, 20040070, 31980526, 26907177) (less)
|
|
|
Pathogenic
(Feb 05, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV002018199.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
|
|
|
Pathogenic
(Jan 29, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Charcot-Marie-Tooth disease axonal type 2V
Mucopolysaccharidosis, MPS-III-B
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000813973.5
First in ClinVar: Oct 10, 2018 Last updated: Feb 28, 2024 |
Comment:
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). … (more)
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). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change affects NAGLU function (PMID: 21712855). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(Feb 25, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Mucopolysaccharidosis, MPS-III-B
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
unknown
|
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV002102467.2
First in ClinVar: Mar 05, 2022 Last updated: Oct 13, 2024 |
Clinical Features:
Abnormal temper tantrums (present) , Atypical behavior (present) , Abnormality of the face (present) , Reduced level of N-acetylglucosaminyltransferase II (present) , Intellectual disability, borderline … (more)
Abnormal temper tantrums (present) , Atypical behavior (present) , Abnormality of the face (present) , Reduced level of N-acetylglucosaminyltransferase II (present) , Intellectual disability, borderline (present) (less)
Sex: female
|
|
|
Pathogenic
(Apr 22, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Mucopolysaccharidosis, MPS-III-B
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Pittsburgh Clinical Genomics Laboratory, University of Pittsburgh Medical Center
Accession: SCV005397724.1
First in ClinVar: Nov 17, 2024 Last updated: Nov 17, 2024 |
Comment:
This sequence variant is a single nucleotide substitution (A>G) at position 1834 of the coding sequence of the NAGLU gene that results in a serine … (more)
This sequence variant is a single nucleotide substitution (A>G) at position 1834 of the coding sequence of the NAGLU gene that results in a serine to glycine amino acid change at residue 612 of the N-acetyl-alpha-glucosaminidase protein. The 612 residue falls in the alpha-N-acetylglucosaminidase domain (UniProt). This is a previously reported variant (ClinVar 522823) that is one of the most commonly observed variants in individuals affected by attenuated mucopolysaccharidosis type IIIB (PMID: 34743503, 9443875, 20852935, 20040070, 26907177). In addition, this variant, while in the compound heterozygous state, cosegregates with attenuated mucopolysaccharidosis type IIIB in a family with four affected siblings (PMID: 21712855). This variant is present in 32 of 373546 alleles (0.0086%) in the gnomAD population dataset. Multiple bioinformatic tools predict that this amino acid change would be damaging, and the Ser612 residue at this position is highly conserved across the vertebrate species examined. In addition, the enzymatic activity of the protein generated from this variant in transfected fibroblasts is significantly reduced relative to the wildtype protein (PMID: 26907177, 29979746, 28751108). Based upon the evidence, we consider this a pathogenic variant. ACMG Criteria: PM3, PP1, PP3, PS3, PS4 (less)
|
|
|
Pathogenic
(Sep 16, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Mucopolysaccharidosis type IIIB
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV001463392.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
|
|
|
not provided
(-)
|
no classification provided
Method: literature only
|
Mucopolysaccharidosis
Affected status: unknown
Allele origin:
germline
|
GeneReviews
Accession: SCV001194298.2
First in ClinVar: Apr 06, 2020 Last updated: Oct 01, 2022 |
|
|
| click to load more click to collapse | |||||
Comment:
Comment:
Published functional studies demonstrate a damaging effect, as the variant results in loss of enzyme activity (Clark et al., 2018); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29979746, 28751108, 20852935, 9443875, 35848209, 31718697, 34347683, 25256447, 21712855, 20040070, 31980526, 26907177)
Comment:
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). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change affects NAGLU function (PMID: 21712855). For these reasons, this variant has been classified as Pathogenic.
Comment:
This sequence variant is a single nucleotide substitution (A>G) at position 1834 of the coding sequence of the NAGLU gene that results in a serine to glycine amino acid change at residue 612 of the N-acetyl-alpha-glucosaminidase protein. The 612 residue falls in the alpha-N-acetylglucosaminidase domain (UniProt). This is a previously reported variant (ClinVar 522823) that is one of the most commonly observed variants in individuals affected by attenuated mucopolysaccharidosis type IIIB (PMID: 34743503, 9443875, 20852935, 20040070, 26907177). In addition, this variant, while in the compound heterozygous state, cosegregates with attenuated mucopolysaccharidosis type IIIB in a family with four affected siblings (PMID: 21712855). This variant is present in 32 of 373546 alleles (0.0086%) in the gnomAD population dataset. Multiple bioinformatic tools predict that this amino acid change would be damaging, and the Ser612 residue at this position is highly conserved across the vertebrate species examined. In addition, the enzymatic activity of the protein generated from this variant in transfected fibroblasts is significantly reduced relative to the wildtype protein (PMID: 26907177, 29979746, 28751108). Based upon the evidence, we consider this a pathogenic variant. ACMG Criteria: PM3, PP1, PP3, PS3, PS4
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
The NAGLU c.1834A>G (p.Ser612Gly) variant has been reported in four studies and in a total of 11 probands with mucopolysaccharidosis including ten probands in a compound heterozygous state and one proband in a homozygous state (Zhao et al. 1998; Verhoeven et al. 2010; Valstar et al. 2010; Selmer et al. 2012). Segregation analysis confirmed co-segregation with disease in a clear autosomal recessive inheritance pattern in two families (Zhao et al. 1998; Selmer et al. 2012). Control data are unavailable for this variant, which is reported at a frequency of 0.00022 in the European (non-Finnish) population of the Exome Aggregation Consortium. Two studies demonstrated deficient alpha-N-acetyl glucosaminidase (NAGLU) enzyme activity in cultured fibroblasts from affected subjects (Verhoeven et al. 2010; Selmer et al. 2012). In five of the six families reported, this variant was associated with an attenuated phenotype of MPS IIIB with a slower progression of disease. Based on the collective evidence the p.Ser612Gly variant is classified as a pathogenic variant for mucopolysaccharidosis type III. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Comment:
Published functional studies demonstrate a damaging effect, as the variant results in loss of enzyme activity (Clark et al., 2018); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29979746, 28751108, 20852935, 9443875, 35848209, 31718697, 34347683, 25256447, 21712855, 20040070, 31980526, 26907177)
Comment:
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). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change affects NAGLU function (PMID: 21712855). For these reasons, this variant has been classified as Pathogenic.
Comment:
This sequence variant is a single nucleotide substitution (A>G) at position 1834 of the coding sequence of the NAGLU gene that results in a serine to glycine amino acid change at residue 612 of the N-acetyl-alpha-glucosaminidase protein. The 612 residue falls in the alpha-N-acetylglucosaminidase domain (UniProt). This is a previously reported variant (ClinVar 522823) that is one of the most commonly observed variants in individuals affected by attenuated mucopolysaccharidosis type IIIB (PMID: 34743503, 9443875, 20852935, 20040070, 26907177). In addition, this variant, while in the compound heterozygous state, cosegregates with attenuated mucopolysaccharidosis type IIIB in a family with four affected siblings (PMID: 21712855). This variant is present in 32 of 373546 alleles (0.0086%) in the gnomAD population dataset. Multiple bioinformatic tools predict that this amino acid change would be damaging, and the Ser612 residue at this position is highly conserved across the vertebrate species examined. In addition, the enzymatic activity of the protein generated from this variant in transfected fibroblasts is significantly reduced relative to the wildtype protein (PMID: 26907177, 29979746, 28751108). Based upon the evidence, we consider this a pathogenic variant. ACMG Criteria: PM3, PP1, PP3, PS3, PS4
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Mucopolysaccharidosis III: Molecular basis and treatment. | Spahiu L | Pediatric endocrinology, diabetes, and metabolism | 2021 | PMID: 34743503 |
| Utilizing ExAC to assess the hidden contribution of variants of unknown significance to Sanfilippo Type B incidence. | Clark WT | PloS one | 2018 | PMID: 29979746 |
| Processing of mutant N-acetyl-α-glucosaminidase in mucopolysaccharidosis type IIIB fibroblasts cultured at low temperature. | Meijer OLM | Molecular genetics and metabolism | 2017 | PMID: 28751108 |
| Residual N-acetyl-α-glucosaminidase activity in fibroblasts correlates with disease severity in patients with mucopolysaccharidosis type IIIB. | Meijer OLM | Journal of inherited metabolic disease | 2016 | PMID: 26907177 |
| Early Umbilical Cord Blood-Derived Stem Cell Transplantation Does Not Prevent Neurological Deterioration in Mucopolysaccharidosis Type III. | Welling L | JIMD reports | 2015 | PMID: 25256447 |
| A mild form of Mucopolysaccharidosis IIIB diagnosed with targeted next-generation sequencing of linked genomic regions. | Selmer KK | European journal of human genetics : EJHG | 2012 | PMID: 21712855 |
| Mucopolysaccharidosis type IIIB may predominantly present with an attenuated clinical phenotype. | Valstar MJ | Journal of inherited metabolic disease | 2010 | PMID: 20852935 |
| Sanfilippo B in an elderly female psychiatric patient: a rare but relevant diagnosis in presenile dementia. | Verhoeven WM | Acta psychiatrica Scandinavica | 2010 | PMID: 20040070 |
| Genotype-phenotype correspondence in Sanfilippo syndrome type B. | Zhao HG | American journal of human genetics | 1998 | PMID: 9443875 |
Text-mined citations for rs148881970 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Nov 19, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.