NM_000203.5(IDUA):c.784del (p.His262fs) AND Mucopolysaccharidosis type 1

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 6, 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:: RCV001229775.8

Allele description [Variation Report for NM_000203.5(IDUA):c.784del (p.His262fs)]

NM_000203.5(IDUA):c.784del (p.His262fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

4p16.3

Genomic location:

Preferred name:

NM_000203.5(IDUA):c.784del (p.His262fs)

Other names:

p.His262ThrfsTer5

HGVS:

NC_000004.12:g.1001873del
NG_008103.1:g.19877del
NM_000203.5:c.784delMANE SELECT
NM_001363576.1:c.388del
NP_000194.2:p.His262fs
NP_001350505.1:p.His130fs
LRG_1277t1:c.784del
LRG_1277:g.19877del
LRG_1277p1:p.His262fs
NC_000004.11:g.995660del
NC_000004.11:g.995661del
NM_000203.4:c.784del
NR_110313.1:n.872del

Protein change:

H130fs

Links:

dbSNP: rs757928590

NCBI 1000 Genomes Browser:

rs757928590

Molecular consequence:

NM_000203.5:c.784del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001363576.1:c.388del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_110313.1:n.872del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Functional consequence:

protein truncation [Variation Ontology: 0015]

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

Recent activity

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protachykinin-1 isoform delta precursor [Homo sapiens]
protachykinin-1 isoform delta precursor [Homo sapiens]
gi|7770079|ref|NP_054704.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001402231	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 6, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11735025, 21480867, 27146977, 28492532
SCV002075311	Natera, Inc.	no assertion criteria provided	Pathogenic (Sep 24, 2021)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001402231

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 6, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV002075311

Natera, Inc.

no assertion criteria provided

Pathogenic
(Sep 24, 2021)

germline

clinical testing

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

Mucopolysaccharidosis I mutations in Chinese patients: identification of 27 novel mutations and 6 cases involving prenatal diagnosis.

Wang X, Zhang W, Shi H, Qiu Z, Meng Y, Yao F, Wei M.

Clin Genet. 2012 May;81(5):443-52. doi: 10.1111/j.1399-0004.2011.01680.x. Epub 2011 May 16. Erratum in: Clin Genet. 2012 May;81(5):501.

PubMed [citation]

PMID:: 21480867

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001402231.5

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

Description

This sequence change creates a premature translational stop signal (p.His262Thrfs*55) in the IDUA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in IDUA are known to be pathogenic (PMID: 11735025, 21480867). This variant is present in population databases (rs757928590, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with mucopolysaccharidosis type I (PMID: 27146977). ClinVar contains an entry for this variant (Variation ID: 956890). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as 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

From Natera, Inc., SCV002075311.1

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

Last Updated: Oct 20, 2024

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