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NM_000199.5(SGSH):c.892T>C (p.Ser298Pro) AND Sanfilippo syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 2, 2017
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:
RCV000326423.10

Allele description [Variation Report for NM_000199.5(SGSH):c.892T>C (p.Ser298Pro)]

NM_000199.5(SGSH):c.892T>C (p.Ser298Pro)

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.892T>C (p.Ser298Pro)
HGVS:
  • NC_000017.11:g.80212128A>G
  • NG_008229.1:g.13273T>C
  • NM_000199.5:c.892T>CMANE SELECT
  • NM_001352921.3:c.892T>C
  • NM_001352922.2:c.892T>C
  • NP_000190.1:p.Ser298Pro
  • NP_000190.1:p.Ser298Pro
  • NP_001339850.1:p.Ser298Pro
  • NP_001339851.1:p.Ser298Pro
  • NC_000017.10:g.78185927A>G
  • NM_000199.3:c.892T>C
  • NM_000199.4:c.892T>C
  • NR_148201.2:n.806T>C
  • P51688:p.Ser298Pro
  • p.S298P
Protein change:
S298P; SER298PRO
Links:
UniProtKB: P51688#VAR_007412; OMIM: 605270.0013; dbSNP: rs138504221
NCBI 1000 Genomes Browser:
rs138504221
Molecular consequence:
  • NM_000199.5:c.892T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352921.3:c.892T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352922.2:c.892T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148201.2:n.806T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000695961Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Aug 2, 2017) 		germlineclinical testing

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

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Residual activity and proteasomal degradation of p.Ser298Pro sulfamidase identified in patients with a mild clinical phenotype of Sanfilippo A syndrome.

Muschol N, Pohl S, Meyer A, Gal A, Ullrich K, Braulke T.

Am J Med Genet A. 2011 Jul;155A(7):1634-9. doi: 10.1002/ajmg.a.34053. Epub 2011 Jun 10.

PubMed [citation]
PMID:
21671382

Molecular characterization of 355 mucopolysaccharidosis patients reveals 104 novel mutations.

Pollard LM, Jones JR, Wood TC.

J Inherit Metab Dis. 2013 Mar;36(2):179-87. doi: 10.1007/s10545-012-9533-7. Epub 2012 Sep 14.

PubMed [citation]
PMID:
22976768
See all PubMed Citations (6)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000695961.1

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

Description

Variant summary: The SGSH c.892T>C (p.Ser298Pro) variant involves the alteration of a conserved nucleotide that lies within the Alkaline-phosphatase-like, core domain, Sulfatase, N-terminal domain, and Alkaline phosphatase-like, alpha/beta/alpha domain (InterPro). 4/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). Functional studies found no to minimal (2.3% of wild-type) heparin-N sulfatase activity associated with this variant (Pollard_JIMD_2013, Muschol_AJMG_2011). This variant was found in the large control database ExAC and in the literature at a frequency of 0.0000917 (11/120004 control chromosomes), which does not exceed the estimated maximal expected allele frequency of a pathogenic SGSH variant (0.0032275). The variant has been found in numerous MPS IIIA patients, in compound heterozygotes as well as homozygotes, and was reported as being associated with a clinically mild phenotype (Valstar_Mutat_Annals of Neurology_2010, Meyer_HM_2008). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.

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

Last Updated: Nov 10, 2024