NM_000203.5(IDUA):c.617C>T (p.Ser206Leu) AND Mucopolysaccharidosis type 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 1, 2022
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:: RCV002002109.5

Allele description [Variation Report for NM_000203.5(IDUA):c.617C>T (p.Ser206Leu)]

NM_000203.5(IDUA):c.617C>T (p.Ser206Leu)

Gene:

IDUA:alpha-L-iduronidase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4p16.3

Genomic location:

Preferred name:

NM_000203.5(IDUA):c.617C>T (p.Ser206Leu)

HGVS:

NC_000004.12:g.1001706C>T
NG_008103.1:g.19710C>T
NM_000203.5:c.617C>TMANE SELECT
NM_001363576.1:c.221C>T
NP_000194.2:p.Ser206Leu
NP_001350505.1:p.Ser74Leu
LRG_1277t1:c.617C>T
LRG_1277:g.19710C>T
LRG_1277p1:p.Ser206Leu
NC_000004.11:g.995494C>T
NR_110313.1:n.705C>T

Protein change:

S206L

Links:

dbSNP: rs756131787

NCBI 1000 Genomes Browser:

rs756131787

Molecular consequence:

NM_000203.5:c.617C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001363576.1:c.221C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_110313.1:n.705C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Mucopolysaccharidosis type 1
Synonyms:: Mucopolysaccharidosis type I; MPS 1; Attenuated MPS I (subtype); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0001586; MedGen: C0023786

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002217193	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 1, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29801497, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002217193

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 1, 2022)

germline

clinical testing

PubMed (2)
[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

Status of newborn screening and follow up investigations for Mucopolysaccharidoses I and II in Taiwan.

Chuang CK, Lin HY, Wang TJ, Huang YH, Chan MJ, Liao HC, Lo YT, Wang LY, Tu RY, Fang YY, Chen TL, Ho HC, Chiang CC, Lin SP.

Orphanet J Rare Dis. 2018 May 25;13(1):84. doi: 10.1186/s13023-018-0816-4.

PubMed [citation]

PMID:: 29801497
PMCID:: PMC5970538

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002217193.2

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

Description

This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 206 of the IDUA protein (p.Ser206Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with mucopolysaccharidosis type I (PMID: 29801497). ClinVar contains an entry for this variant (Variation ID: 1436435). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt IDUA protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Sep 29, 2024

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