NM_000203.5(IDUA):c.1713del (p.Glu571fs) AND Mucopolysaccharidosis type 1

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 9, 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:: RCV002815878.2

Allele description

NM_000203.5(IDUA):c.1713del (p.Glu571fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

4p16.3

Genomic location:

Preferred name:

NM_000203.5(IDUA):c.1713del (p.Glu571fs)

HGVS:

NC_000004.12:g.1003611del
NG_008103.1:g.21615del
NG_101700.1:g.500del
NM_000203.5:c.1713delMANE SELECT
NM_001363576.1:c.1317del
NP_000194.2:p.Glu571fs
NP_001350505.1:p.Glu439fs
LRG_1277t1:c.1713del
LRG_1277:g.21615del
LRG_1277p1:p.Glu571fs
NC_000004.11:g.997398del
NC_000004.11:g.997399del
NR_110313.1:n.1801del

Protein change:

E439fs

Molecular consequence:

NM_000203.5:c.1713del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001363576.1:c.1317del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_110313.1:n.1801del - 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
SCV003210577	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 9, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 11735025, 16438163, 21480867, 26825088, 27146977, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003210577

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 9, 2022)

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

Mutational analysis of 85 mucopolysaccharidosis type I families: frequency of known mutations, identification of 17 novel mutations and in vitro expression of missense mutations.

Beesley CE, Meaney CA, Greenland G, Adams V, Vellodi A, Young EP, Winchester BG.

Hum Genet. 2001 Nov;109(5):503-11. Epub 2001 Oct 19.

PubMed [citation]

PMID:: 11735025

The molecular basis of mucopolysaccharidosis type I in two Thai patients.

Ketudat Cairns JR, Keeratichamroen S, Sukcharoen S, Champattanachai V, Ngiwsara L, Lirdprapamongkol K, Liammongkolkul S, Srisomsap C, Surarit R, Wasant P, Svasti J.

Southeast Asian J Trop Med Public Health. 2005 Sep;36(5):1308-12.

PubMed [citation]

PMID:: 16438163

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV003210577.2

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the IDUA protein in which other variant(s) (p.Ser633Leu) have been determined to be pathogenic (PMID: 11735025, 16438163, 21480867, 26825088, 27146977). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with IDUA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the IDUA gene (p.Glu571Aspfs*?). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 83 amino acid(s) of the IDUA protein and extend the protein by an uncertain number of additional amino acid residues.

#	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 1, 2024

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