NM_000199.5(SGSH):c.1241_1242dup (p.Thr415fs) AND Mucopolysaccharidosis, MPS-III-A

Clinical significance:Pathogenic (Last evaluated: Jan 13, 2020)

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.1241_1242dup (p.Thr415fs)]

NM_000199.5(SGSH):c.1241_1242dup (p.Thr415fs)

SGSH:N-sulfoglucosamine sulfohydrolase [Gene - OMIM - HGNC]
Variant type:
Cytogenetic location:
Genomic location:
Preferred name:
NM_000199.5(SGSH):c.1241_1242dup (p.Thr415fs)
  • NC_000017.11:g.80210720_80210721dup
  • NG_008229.1:g.14681_14682dup
  • NG_032778.1:g.45729_45730dup
  • NM_000199.5:c.1241_1242dupMANE SELECT
  • NM_001352921.3:c.*328_*329dup
  • NM_001352922.2:c.*291_*292dup
  • NP_000190.1:p.Thr415fs
  • LRG_1330:g.45729_45730dup
  • NC_000017.10:g.78184517_78184518insGC
  • NC_000017.10:g.78184519_78184520dup
  • NR_148201.2:n.1155_1156dup
Protein change:
Molecular consequence:
  • NM_001352921.3:c.*328_*329dup - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001352922.2:c.*291_*292dup - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000199.5:c.1241_1242dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NR_148201.2:n.1155_1156dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]


Mucopolysaccharidosis, MPS-III-A (MPS3A)
SULFAMIDASE DEFICIENCY; Mucopoly-saccharidosis type 3A; Sanfilippo syndrome A; See all synonyms [MedGen]
MONDO: MONDO:0009655; MedGen: C0086647; Orphanet: 581; Orphanet: 79269; OMIM: 252900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV001586523Invitaecriteria provided, single submitter
(Jan 13, 2020)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

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



Cloning of the sulphamidase gene and identification of mutations in Sanfilippo A syndrome.

Scott HS, Blanch L, Guo XH, Freeman C, Orsborn A, Baker E, Sutherland GR, Morris CP, Hopwood JJ.

Nat Genet. 1995 Dec;11(4):465-7.

PubMed [citation]

A prospective one-year natural history study of mucopolysaccharidosis types IIIA and IIIB: Implications for clinical trial design.

Truxal KV, Fu H, McCarty DM, McNally KA, Kunkler KL, Zumberge NA, Martin L, Aylward SC, Alfano LN, Berry KM, Lowes LP, Corridore M, McKee C, McBride KL, Flanigan KM.

Mol Genet Metab. 2016 Nov;119(3):239-248. doi: 10.1016/j.ymgme.2016.08.002. Epub 2016 Aug 18.

PubMed [citation]
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001586523.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)


This sequence change results in a frameshift in the SGSH gene (p.Thr415Alafs*177). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 88 amino acids of the SGSH protein and extend the protein by an additional 88 amino acids. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SGSH-related conditions. This variant disrupts the C-terminus of the SGSH protein. Other variant(s) that disrupt this region (p.Tyr424*) have been determined to be pathogenic (PMID: 7493035, 27590925). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: May 14, 2021

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