NM_000199.5(SGSH):c.545G>A (p.Arg182His) AND Mucopolysaccharidosis, MPS-III-A

Clinical significance:Pathogenic (Last evaluated: Oct 8, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001384263.1

Allele description [Variation Report for NM_000199.5(SGSH):c.545G>A (p.Arg182His)]

NM_000199.5(SGSH):c.545G>A (p.Arg182His)

Gene:
SGSH:N-sulfoglucosamine sulfohydrolase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q25.3
Genomic location:
Preferred name:
NM_000199.5(SGSH):c.545G>A (p.Arg182His)
HGVS:
  • NC_000017.11:g.80214290C>T
  • NG_008229.1:g.11111G>A
  • NM_000199.5:c.545G>AMANE SELECT
  • NM_001352921.3:c.545G>A
  • NM_001352922.2:c.545G>A
  • NP_000190.1:p.Arg182His
  • NP_001339850.1:p.Arg182His
  • NP_001339851.1:p.Arg182His
  • NC_000017.10:g.78188089C>T
  • NR_148201.2:n.459G>A
Protein change:
R182H
Molecular consequence:
  • NM_000199.5:c.545G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352921.3:c.545G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352922.2:c.545G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148201.2:n.459G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Mucopolysaccharidosis, MPS-III-A (MPS3A)
Synonyms:
SULFAMIDASE DEFICIENCY; Mucopoly-saccharidosis type 3A; Sanfilippo syndrome A; See all synonyms [MedGen]
Identifiers:
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)
OriginMethodCitations
SCV001583692Invitaecriteria provided, single submitter
Pathogenic
(Oct 8, 2020)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

The attenuated end of the phenotypic spectrum in MPS III: from late-onset stable cognitive impairment to a non-neuronopathic phenotype.

Nijmeijer SCM, van den Born LI, Kievit AJA, Stepien KM, Langendonk J, Marchal JP, Roosing S, Wijburg FA, Wagenmakers MAEM.

Orphanet J Rare Dis. 2019 Nov 12;14(1):249. doi: 10.1186/s13023-019-1232-0.

PubMed [citation]
PMID:
31718697
PMCID:
PMC6852993

Mucopolysaccharidosis type IIIA: clinical spectrum and genotype-phenotype correlations.

Valstar MJ, Neijs S, Bruggenwirth HT, Olmer R, Ruijter GJ, Wevers RA, van Diggelen OP, Poorthuis BJ, Halley DJ, Wijburg FA.

Ann Neurol. 2010 Dec;68(6):876-87. doi: 10.1002/ana.22092.

PubMed [citation]
PMID:
21061399
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV001583692.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change replaces arginine with histidine at codon 182 of the SGSH protein (p.Arg182His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs372911015, ExAC 0.01%). This variant has been observed in individual(s) with mucopolysaccharidosis type III (PMID: 31718697). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). This variant disrupts the p.Arg182 amino acid residue in SGSH. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21061399, 30809705, 9554748, 10727844). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: May 14, 2021

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