NM_000181.4(GUSB):c.1856C>T (p.Ala619Val) AND Mucopolysaccharidosis type 7

Clinical significance:Pathogenic (Last evaluated: Jan 27, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000000941.4

Allele description [Variation Report for NM_000181.4(GUSB):c.1856C>T (p.Ala619Val)]

NM_000181.4(GUSB):c.1856C>T (p.Ala619Val)

Gene:
GUSB:glucuronidase beta [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q11.21
Genomic location:
Preferred name:
NM_000181.4(GUSB):c.1856C>T (p.Ala619Val)
HGVS:
  • NC_000007.14:g.65960997G>A
  • NG_016197.1:g.26318C>T
  • NG_051954.1:g.92899G>A
  • NM_000181.4:c.1856C>TMANE SELECT
  • NM_001284290.2:c.1418C>T
  • NM_001293104.2:c.1286C>T
  • NM_001293105.2:c.1199C>T
  • NP_000172.2:p.Ala619Val
  • NP_001271219.1:p.Ala473Val
  • NP_001280033.1:p.Ala429Val
  • NP_001280034.1:p.Ala400Val
  • NC_000007.13:g.65425984G>A
  • NR_120531.2:n.1801C>T
  • P08236:p.Ala619Val
Protein change:
A400V; ALA619VAL
Links:
UniProtKB: P08236#VAR_003200; OMIM: 611499.0001; dbSNP: rs121918172
NCBI 1000 Genomes Browser:
rs121918172
Molecular consequence:
  • NM_000181.4:c.1856C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001284290.2:c.1418C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293104.2:c.1286C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293105.2:c.1199C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_120531.2:n.1801C>T - 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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000021091OMIMno assertion criteria providedPathogenic
(Jan 1, 1991)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

SCV001589359Invitaecriteria provided, single submitter
Pathogenic
(Jan 27, 2020)
germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Oral manifestations in patients and dogs with mucopolysaccharidosis Type VII.

Kantaputra PN, Smith LJ, Casal ML, Kuptanon C, Chang YC, Nampoothiri S, Paiyarom A, Veerasakulwong T, Trachoo O, Ketudat Cairns JR, Chinadet W, Tanpaiboon P.

Am J Med Genet A. 2019 Mar;179(3):486-493. doi: 10.1002/ajmg.a.61034. Epub 2019 Jan 17.

PubMed [citation]
PMID:
30653816
PMCID:
PMC6374205

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 (7)

Details of each submission

From OMIM, SCV000021091.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a 24-year-old Japanese man with mucopolysaccharidosis type VII (MPS7; 253220), Tomatsu et al. (1991) identified a homozygous C-to-T transition in the GUSB gene, resulting in an ala619-to-val (A619V) substitution in a highly conserved region among human, rat, and E. coli. In vitro functional expression studies showed that the mutant protein resulted in decreased enzyme activity. The change resulted in loss of the cleavage site for Fnu4HI in the mutated cDNA. The patient had unusual facies, hepatomegaly, umbilical herniation, short stature, slight bone deformity, mental retardation, and coarse metachromatic granules in white blood cells. Beta-glucuronidase activity was about 2% of normal values.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001589359.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

This sequence change replaces alanine with valine at codon 619 of the GUSB protein (p.Ala619Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs121918172, ExAC 0.001%). This variant has been observed in individual(s) with mucopolysaccharidosis Type VII (PMID: 1779626, 2115490, 30653816). ClinVar contains an entry for this variant (Variation ID: 893). This variant has been reported to affect GUSB protein function (PMID: 2115490, 1702266, 7633414, 19224584, 1779626). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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