NM_000181.4(GUSB):c.1798dup (p.Arg600fs) AND Mucopolysaccharidosis type 7

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 9, 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:: RCV003828017.2

Allele description [Variation Report for NM_000181.4(GUSB):c.1798dup (p.Arg600fs)]

NM_000181.4(GUSB):c.1798dup (p.Arg600fs)

Gene:

GUSB:glucuronidase beta [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

7q11.21

Genomic location:

Preferred name:

NM_000181.4(GUSB):c.1798dup (p.Arg600fs)

HGVS:

NC_000007.14:g.65961055dup
NG_016197.1:g.26260dup
NG_051954.1:g.92957dup
NG_051954.2:g.100285dup
NM_000181.4:c.1798dupMANE SELECT
NM_001284290.2:c.1360dup
NM_001293104.2:c.1228dup
NM_001293105.2:c.1141dup
NP_000172.2:p.Arg600fs
NP_001271219.1:p.Arg454fs
NP_001280033.1:p.Arg410fs
NP_001280034.1:p.Arg381fs
NC_000007.13:g.65426041_65426042insT
NC_000007.13:g.65426042dup
NR_120531.2:n.1743dup

Protein change:

R381fs

Molecular consequence:

NM_000181.4:c.1798dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001284290.2:c.1360dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001293104.2:c.1228dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001293105.2:c.1141dup - frameshift variant - [Sequence Ontology: SO:0001589]
NR_120531.2:n.1743dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Mucopolysaccharidosis type 7 (MPS7)
Synonyms:: MPS VII; Mucopolysaccharidosis type VII; MPS 7; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009662; MedGen: C0085132; Orphanet: 584; OMIM: 253220

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004621638	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 9, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 1779626, 2115490, 30653816, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004621638

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 9, 2023)

germline

clinical testing

PubMed (4)
[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

Molecular analysis of mucopolysaccharidosis type VII.

Fukuda S, Tomatsu S, Sukegawa K, Sasaki T, Yamada Y, Kuwahara T, Okamoto H, Ikedo Y, Yamaguchi S, Orii T.

J Inherit Metab Dis. 1991;14(5):800-4. No abstract available.

PubMed [citation]

PMID:: 1779626

Molecular basis of mucopolysaccharidosis type VII: replacement of Ala619 in beta-glucuronidase with Val.

Tomatsu S, Sukegawa K, Ikedo Y, Fukuda S, Yamada Y, Sasaki T, Okamoto H, Kuwabara T, Orii T.

Gene. 1990 May 14;89(2):283-7.

PubMed [citation]

PMID:: 2115490

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004621638.1

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the GUSB protein in which other variant(s) (p.Ala619Val) have been determined to be pathogenic (PMID: 1779626, 2115490, 30653816). 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 GUSB-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg600Lysfs*6) in the GUSB gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 52 amino acid(s) of the GUSB protein.

#	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

ClinVar

Relating variation to medicine