NM_000203.5(IDUA):c.-23_18del (p.Met1fs) AND Mucopolysaccharidosis type 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 22, 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:: RCV003755969.1

Allele description [Variation Report for NM_000203.5(IDUA):c.-23_18del (p.Met1fs)]

NM_000203.5(IDUA):c.-23_18del (p.Met1fs)

Genes:

IDUA:alpha-L-iduronidase [Gene - OMIM - HGNC]
SLC26A1:solute carrier family 26 member 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

4p16.3

Genomic location:

Preferred name:

NM_000203.5(IDUA):c.-23_18del (p.Met1fs)

HGVS:

NC_000004.12:g.987062_987102del
NG_008103.1:g.5066_5106del
NG_033042.1:g.11340_11380del
NG_158244.2:g.262_302del
NM_000203.5:c.-23_18delMANE SELECT
NM_134425.4:c.576+4031_576+4071del
NP_000194.2:p.Met1fs
LRG_1277t1:c.-23_18del
LRG_1277:g.5066_5106del
LRG_1277p1:p.Met1fs
NC_000004.11:g.980845_980885del
NC_000004.11:g.980850_980890del
NR_110313.1:n.66_106del

Protein change:

M1fs

Molecular consequence:

NM_000203.5:c.-23_18del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_000203.5:c.-23_18del - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_134425.4:c.576+4031_576+4071del - intron variant - [Sequence Ontology: SO:0001627]
NR_110313.1:n.66_106del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Mucopolysaccharidosis type 1 (MPS1)
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
SCV004469148	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 22, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31236806, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004469148

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 22, 2023)

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

Genetic testing of Mucopolysaccharidoses disease using multiplex PCR- based panels of STR markers: in silico analysis of novel mutations.

Shafaat M, Hashemi M, Majd A, Abiri M, Zeinali S.

Metab Brain Dis. 2019 Oct;34(5):1447-1455. doi: 10.1007/s11011-019-00434-z. Epub 2019 Jun 24.

PubMed [citation]

PMID:: 31236806

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 Invitae, SCV004469148.1

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

Description

For these reasons, this variant has been classified as Pathogenic. Disruption of the initiator codon has been observed in individual(s) with mucopolysaccharidosis type I (PMID: 31236806). This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the IDUA mRNA. The next in-frame methionine is located at codon 133.

#	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: Jul 29, 2024

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