NM_000199.5(SGSH):c.1135del (p.Val379fs) AND Sanfilippo syndrome

Clinical significance:Pathogenic (Last evaluated: Jun 14, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_000199.5(SGSH):c.1135del (p.Val379fs)]

NM_000199.5(SGSH):c.1135del (p.Val379fs)

SGSH:N-sulfoglucosamine sulfohydrolase [Gene - OMIM - HGNC]
Variant type:
Cytogenetic location:
Genomic location:
Preferred name:
NM_000199.5(SGSH):c.1135del (p.Val379fs)
  • NC_000017.11:g.80210826del
  • NG_008229.1:g.14575del
  • NG_032778.1:g.45835del
  • NM_000199.5:c.1135delMANE SELECT
  • NM_001352921.2:c.*222del
  • NM_001352922.2:c.*185del
  • NP_000190.1:p.Val379fs
  • LRG_1330:g.45835del
  • NC_000017.10:g.78184625del
  • NM_000199.3:c.1135delG
  • NR_148201.2:n.1049del
Protein change:
dbSNP: rs777956287
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001352921.2:c.*222del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001352922.2:c.*185del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000199.5:c.1135del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NR_148201.2:n.1049del - non-coding transcript variant - [Sequence Ontology: SO:0001619]


Sanfilippo syndrome
Mucopolysaccharidosis type III; Mucopoly-saccharidosis type 3; Mucopolysaccharidosis type 3; See all synonyms [MedGen]
MONDO: MONDO:0018937; MedGen: C0026706

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000407348Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
(Jun 14, 2016)
germlineclinical testing

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


Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing



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]

Transport, enzymatic activity, and stability of mutant sulfamidase (SGSH) identified in patients with mucopolysaccharidosis type III A.

Muschol N, Storch S, Ballhausen D, Beesley C, Westermann JC, Gal A, Ullrich K, Hopwood JJ, Winchester B, Braulke T.

Hum Mutat. 2004 Jun;23(6):559-66.

PubMed [citation]
See all PubMed Citations (4)

Details of each submission

From Illumina Clinical Services Laboratory,Illumina, SCV000407348.2

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


The c.1135delG (p.Val379CysfsTer34) variant (also known as delG1147) results in a frameshift, and is predicted to result in premature termination of the protein. The p.Val379CysfsTer variant has been identified in at least six patients with mucopolysaccharidosis type III, including one in a homozygous state and five in a compound heterozygous state (Weber et al. 1997; Muschol et al. 2004; Chistiakov et al. 2014). Control data are unavailable for this variant, which is not found in the 1000 Genomes Project, the Exome Sequencing Project, or the Exome Aggregation Consortium. Muschol et al. (2004) demonstrated that the p.Val379CysfsTer34 variant protein is degraded in the endoplasmic reticulum prior to the sorting site in the Golgi apparatus. In addition, Chistiakov et al. (2014) showed that the variant resulted in markedly reduced enzyme activity in patients compared to control levels. Patients who were compound heterozygous for the p.Val379CysfsTer34 variant and a common missense variant (p.Arg74Cys), had residual SGSH activity which was intermediate between the enzymatic activity in individuals who were homozygous for the p.Arg74Cys variant and those who were compound heterozygous for the p.Arg74Cys variant. Due to the potential impact of frameshift variants and the supporting evidence from the literature, the p.Val379CysfsTer34 variant is classified as pathogenic for mucopolysaccharidosis type III.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2021

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