NM_000202.8(IDS):c.998C>T (p.Ser333Leu) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 5, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000790725.14

Allele description [Variation Report for NM_000202.8(IDS):c.998C>T (p.Ser333Leu)]

NM_000202.8(IDS):c.998C>T (p.Ser333Leu)

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.998C>T (p.Ser333Leu)

HGVS:

NC_000023.11:g.149490322G>A
NG_011900.3:g.20013C>T
NG_042264.1:g.3677G>A
NM_000202.8:c.998C>TMANE SELECT
NM_001166550.4:c.728C>T
NM_006123.5:c.998C>T
NP_000193.1:p.Ser333Leu
NP_000193.1:p.Ser333Leu
NP_001160022.1:p.Ser243Leu
NP_006114.1:p.Ser333Leu
NC_000023.10:g.148571853G>A
NM_000202.4:c.998C>T
NM_000202.5:c.998C>T
NM_000202.6:c.998C>T
NR_104128.2:n.1297C>T
P22304:p.Ser333Leu

Protein change:

S243L; SER333LEU

Links:

UniProtKB: P22304#VAR_007360; OMIM: 300823.0002; dbSNP: rs104894853

NCBI 1000 Genomes Browser:

rs104894853

Molecular consequence:

NM_000202.8:c.998C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001166550.4:c.728C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_006123.5:c.998C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_104128.2:n.1297C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Functional consequence:

variation affecting protein [Variation Ontology: 0002]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000232028	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions)	Pathogenic (Aug 29, 2013)	germline	clinical testing	Citation Link,
SCV002578620	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Oct 5, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000232028

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions)

Pathogenic
(Aug 29, 2013)

germline

clinical testing

Citation Link,

SCV002578620

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Oct 5, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	4	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From Eurofins Ntd Llc (ga), SCV000232028.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	4	not provided	not provided	clinical testing	not provided

#	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		4	not provided	not provided	not provided

From GeneDx, SCV002578620.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Published functional studies with S333L transfected into CHO, HEK293T, and COS-7 cells indicate a severe impairment of protein function (Sukegawa-Hayasaka et al., 2006; Vollebregt et al., 2017; Lin et al., 2019); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 16495038, 9921913, 9660053, 27246110, 1639384, 27695081, 30548430, 30639582, 9950361, 27896113, 27883178, 8830188, 28543354, 9875019, 21291454, 21829674, 33676511, 31877959, 34258227, 35144014, 17091340, 24125893)

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

Last Updated: Oct 20, 2024

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