NM_000263.4(NAGLU):c.1772T>C (p.Leu591Pro) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 4, 2019
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:: RCV001193369.1

Allele description [Variation Report for NM_000263.4(NAGLU):c.1772T>C (p.Leu591Pro)]

NM_000263.4(NAGLU):c.1772T>C (p.Leu591Pro)

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.1772T>C (p.Leu591Pro)

HGVS:

NC_000017.11:g.42543778T>C
NG_011552.1:g.12846T>C
NM_000263.4:c.1772T>CMANE SELECT
NP_000254.2:p.Leu591Pro
NC_000017.10:g.40695796T>C
NM_000263.3:c.1772T>C

Protein change:

L591P

Links:

dbSNP: rs1215582852

NCBI 1000 Genomes Browser:

rs1215582852

Molecular consequence:

NM_000263.4:c.1772T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001362137	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Oct 4, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 9832037, 11668611 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001362137

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Oct 4, 2019)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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

Identification of 12 novel mutations in the alpha-N-acetylglucosaminidase gene in 14 patients with Sanfilippo syndrome type B (mucopolysaccharidosis type IIIB).

Beesley CE, Young EP, Vellodi A, Winchester BG.

J Med Genet. 1998 Nov;35(11):910-4.

PubMed [citation]

PMID:: 9832037
PMCID:: PMC1051483

Molecular genetics of mucopolysaccharidosis type IIIA and IIIB: Diagnostic, clinical, and biological implications.

Yogalingam G, Hopwood JJ.

Hum Mutat. 2001 Oct;18(4):264-81. Review.

PubMed [citation]

PMID:: 11668611

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001362137.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: NAGLU c.1772T>C (p.Leu591Pro) results in a non-conservative amino acid change located in the Alpha-N-acetylglucosaminidase, C-terminal of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.2e-06 in 242902 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1772T>C has been reported in the literature in a compound heterozygote individual affected with a severe form of Mucopolysaccharidosis Type IIIB (Sanfilippo Syndrome B)(Beesley_1998). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

#	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: Mar 5, 2024

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