NM_000203.5(IDUA):c.1708G>C (p.Asp570His) AND Mucopolysaccharidosis type 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 17, 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:: RCV002530678.3

Allele description [Variation Report for NM_000203.5(IDUA):c.1708G>C (p.Asp570His)]

NM_000203.5(IDUA):c.1708G>C (p.Asp570His)

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.1708G>C (p.Asp570His)

HGVS:

NC_000004.12:g.1003606G>C
NG_008103.1:g.21610G>C
NM_000203.5:c.1708G>CMANE SELECT
NM_001363576.1:c.1312G>C
NP_000194.2:p.Asp570His
NP_001350505.1:p.Asp438His
LRG_1277t1:c.1708G>C
LRG_1277:g.21610G>C
LRG_1277p1:p.Asp570His
NC_000004.11:g.997394G>C
NM_000203.3:c.1708G>C
NR_110313.1:n.1796G>C

Protein change:

D438H

Links:

dbSNP: rs1553917627

NCBI 1000 Genomes Browser:

rs1553917627

Molecular consequence:

NM_000203.5:c.1708G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001363576.1:c.1312G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_110313.1:n.1796G>C - 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
SCV003525406	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 17, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25558755, 31991612, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003525406

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 17, 2023)

germline

clinical testing

PubMed (3)
[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

Mutation c.1190-1delG/N in intron 8 and c.1708G>C/N in exon 12 not reported in the IDUA gene developed a clinical phenotype of Scheie syndrome.

Delgado Luengo WN, Miranda Contreras LE, Chávez CJ, Solis-Añez E, Cammarata-Scalisi F.

Invest Clin. 2014 Dec;55(4):365-70.

PubMed [citation]

PMID:: 25558755

Respiratory Dysfunction in Children and Adolescents with Mucopolysaccharidosis Types I, II, IVA, and VI.

Tulebayeva A, Sharipova M, Boranbayeva R.

Diagnostics (Basel). 2020 Jan 24;10(2). doi:pii: E63. 10.3390/diagnostics10020063.

PubMed [citation]

PMID:: 31991612
PMCID:: PMC7168931

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003525406.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This missense change has been observed in individual(s) with mucopolysaccharidosis type I (PMID: 25558755). ClinVar contains an entry for this variant (Variation ID: 551300). 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. This variant disrupts the p.Asp570 amino acid residue in IDUA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 31991612). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 570 of the IDUA protein (p.Asp570His).

#	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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