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NM_000199.5(SGSH):c.673T>C (p.Phe225Leu) AND not provided

Clinical significance:Likely pathogenic (Last evaluated: Oct 31, 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.673T>C (p.Phe225Leu)]

NM_000199.5(SGSH):c.673T>C (p.Phe225Leu)

SGSH:N-sulfoglucosamine sulfohydrolase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000199.5(SGSH):c.673T>C (p.Phe225Leu)
  • NC_000017.11:g.80213876A>G
  • NG_008229.1:g.11525T>C
  • NM_000199.5:c.673T>CMANE SELECT
  • NM_001352921.3:c.673T>C
  • NM_001352922.2:c.673T>C
  • NP_000190.1:p.Phe225Leu
  • NP_001339850.1:p.Phe225Leu
  • NP_001339851.1:p.Phe225Leu
  • NC_000017.10:g.78187675A>G
  • NM_000199.3:c.673T>C
  • NR_148201.2:n.587T>C
Protein change:
dbSNP: rs1057521801
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000199.5:c.673T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352921.3:c.673T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001352922.2:c.673T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148201.2:n.587T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]


none provided
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000524593GeneDxcriteria provided, single submitter
Likely pathogenic
(Oct 31, 2016)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000524593.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided


The c.673 T>C nucleotide substitution, resulting in the F225L amino acid change, has not been reported previously as a pathogenic or benign variant to our knowledge. However, a different nucleotide substitution (c.675C>G) that also results in the F225L missense substitution was previously identified in two families with mucopolysaccharidosis type IIIA (MPSIIIA), supporting the functional importance of this position in the protein (Heron et al., 2010). Additionally, a missense variant in a neighboring codon (P227R) has been reported in the Human Gene Mutation Database in association with MPSIIIA (Stenson et al., 2014). The F225L variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. It is a conservative amino acid substitution that occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. The F225L variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.

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

Last Updated: Jul 8, 2022

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