NM_000199.5(SGSH):c.734G>A (p.Arg245His) AND Sanfilippo syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 26, 2016
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:: RCV000348775.10

Allele description [Variation Report for NM_000199.5(SGSH):c.734G>A (p.Arg245His)]

NM_000199.5(SGSH):c.734G>A (p.Arg245His)

Genes:

CARD14:caspase recruitment domain family member 14 [Gene - OMIM - HGNC]
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.734G>A (p.Arg245His)

HGVS:

NC_000017.11:g.80213815C>T
NG_008229.1:g.11586G>A
NM_000199.5:c.734G>AMANE SELECT
NM_001352921.3:c.734G>A
NM_001352922.2:c.734G>A
NP_000190.1:p.Arg245His
NP_000190.1:p.Arg245His
NP_001339850.1:p.Arg245His
NP_001339851.1:p.Arg245His
NC_000017.10:g.78187614C>T
NM_000199.3:c.734G>A
NM_000199.4:c.734G>A
NR_148201.2:n.648G>A
P51688:p.Arg245His

Protein change:

R245H; ARG245HIS

Links:

UniProtKB: P51688#VAR_007411; OMIM: 605270.0001; dbSNP: rs104894635

NCBI 1000 Genomes Browser:

rs104894635

Molecular consequence:

NM_000199.5:c.734G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001352921.3:c.734G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001352922.2:c.734G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_148201.2:n.648G>A - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000695960	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Jun 26, 2016)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 9158154, 9700599 LabCorp Variant Classification Summary - May 2015.docx Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000695960

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Jun 26, 2016)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular defects in Sanfilippo syndrome type A.

Blanch L, Weber B, Guo XH, Scott HS, Hopwood JJ.

Hum Mol Genet. 1997 May;6(5):787-91.

PubMed [citation]

PMID:: 9158154

Identification of a common mutation (R245H) in Sanfilippo A patients from The Netherlands.

Weber B, van de Kamp JJ, Kleijer WJ, Guo XH, Blanch L, van Diggelen OP, Wevers R, Poorthuis BJ, Hopwood JJ.

J Inherit Metab Dis. 1998 Jun;21(4):416-22.

PubMed [citation]

PMID:: 9700599

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000695960.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: The SGSH c.734G>A (p.Arg245His) variant causes a missense change involving a conserved nucleotide with 4/4 in silico tools (SNPs&GO not captured due to low reliability index) predicting a damaging outcome. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 30/72670 (1/2422), which does not exceed the estimated maximal expected allele frequency for a pathogenic SGSH variant of 1/309. The variant of interest has been reported in multiple affected individuals as homozygotes and compound heterozygotes via publications. In addition, multiple reputable databases/clinical laboratories cite the variant as "pathogenic." Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 26, 2024

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