NM_000202.8(IDS):c.1007G>A (p.Gly336Glu) AND Mucopolysaccharidosis, MPS-II

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 5, 2023
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:: RCV003509084.1

Allele description [Variation Report for NM_000202.8(IDS):c.1007G>A (p.Gly336Glu)]

NM_000202.8(IDS):c.1007G>A (p.Gly336Glu)

Genes:

LOC106050102:IDS recombination region [Gene]
IDS:iduronate 2-sulfatase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq28

Genomic location:

Preferred name:

NM_000202.8(IDS):c.1007G>A (p.Gly336Glu)

HGVS:

NC_000023.11:g.149487098C>T
NG_011900.3:g.23237G>A
NG_042264.2:g.454C>T
NM_000202.8:c.1007G>AMANE SELECT
NM_001166550.4:c.737G>A
NP_000193.1:p.Gly336Glu
NP_001160022.1:p.Gly246Glu
NC_000023.10:g.148568629C>T

Protein change:

G246E

Molecular consequence:

NM_000202.8:c.1007G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001166550.4:c.737G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Mucopolysaccharidosis, MPS-II (MPS2)
Synonyms:: Mucopolysaccharidosis type II; Attenuated MPS (subtype; formerly known as mild MPS II); Severe MPS II; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010674; MedGen: C0026705; Orphanet: 580; OMIM: 309900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004299012	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Oct 5, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 9660053, 24454794, 24515576, 16133661, 33960103, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004299012

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Oct 5, 2023)

germline

clinical testing

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

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

Identification of iduronate sulfatase gene alterations in 70 unrelated Hunter patients.

Froissart R, Maire I, Millat G, Cudry S, Birot AM, Bonnet V, Bouton O, Bozon D.

Clin Genet. 1998 May;53(5):362-8.

PubMed [citation]

PMID:: 9660053

The effect of recombinant human iduronate-2-sulfatase (Idursulfase) on growth in young patients with mucopolysaccharidosis type II.

Żuber Z, Różdżyńska-Świątkowska A, Jurecka A, Tylki-Szymańska A.

PLoS One. 2014;9(1):e85074. doi: 10.1371/journal.pone.0085074.

PubMed [citation]

PMID:: 24454794
PMCID:: PMC3890314

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV004299012.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 336 of the IDS protein (p.Gly336Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with mucopolysaccharidosis II (PMID: 9660053, 24454794, 24515576; Invitae). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant disrupts the p.Ala336 amino acid residue in IDS. Other variant(s) that disrupt this residue have been observed in individuals with IDS-related conditions (PMID: 16133661, 33960103), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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: Feb 20, 2024

ClinVar

Relating variation to medicine