NM_000404.4(GLB1):c.176G>A (p.Arg59His) AND Infantile GM1 gangliosidosis

Germline classification:: Pathogenic (5 submissions)
Last evaluated:: Jul 27, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000000995.13

Allele description [Variation Report for NM_000404.4(GLB1):c.176G>A (p.Arg59His)]

NM_000404.4(GLB1):c.176G>A (p.Arg59His)

Gene:

GLB1:galactosidase beta 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p22.3

Genomic location:

Preferred name:

NM_000404.4(GLB1):c.176G>A (p.Arg59His)

HGVS:

NC_000003.12:g.33072613C>T
NG_009005.1:g.29590G>A
NM_000404.4:c.176G>AMANE SELECT
NM_001079811.3:c.86G>A
NM_001135602.3:c.176G>A
NM_001317040.2:c.320G>A
NM_001393580.1:c.176G>A
NP_000395.2:p.Arg59His
NP_000395.3:p.Arg59His
NP_001073279.2:p.Arg29His
NP_001129074.2:p.Arg59His
NP_001303969.2:p.Arg107His
NP_001380509.1:p.Arg59His
NC_000003.11:g.33114105C>T
NM_000404.2:c.176G>A

Protein change:

R107H; ARG59HIS

Links:

OMIM: 611458.0023; dbSNP: rs72555392

NCBI 1000 Genomes Browser:

rs72555392

Molecular consequence:

NM_000404.4:c.176G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001079811.3:c.86G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001135602.3:c.176G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001317040.2:c.320G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001393580.1:c.176G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Infantile GM1 gangliosidosis
Synonyms:: Gangliosidosis, Generalized GM1, Type 1; GM1 gangliosidosis type 1; GM1-gangliosidosis, type I; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009260; MedGen: C0268271; Orphanet: 354; OMIM: 230500

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000021145	OMIM	no assertion criteria provided	Pathogenic (Mar 1, 2007)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 10737981, 17309651
SCV001132205	Counsyl	no assertion criteria provided	Pathogenic (Dec 18, 2017)	unknown	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15714521, 17664528, 16941474, 10338095
SCV001821206	GeneReviews	no classification provided	not provided	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002512229	Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 27, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002579350	MGZ Medical Genetics Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 23, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

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	literature only
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

beta-galactosidase gene mutations affecting the lysosomal enzyme and the elastin-binding protein in GM1-gangliosidosis patients with cardiac involvement.

Morrone A, Bardelli T, Donati MA, Giorgi M, Di Rocco M, Gatti R, Parini R, Ricci R, Taddeucci G, D'Azzo A, Zammarchi E.

Hum Mutat. 2000;15(4):354-66.

PubMed [citation]

PMID:: 10737981

Identification of 14 novel GLB1 mutations, including five deletions, in 19 patients with GM1 gangliosidosis from South America.

Santamaria R, Blanco M, Chabás A, Grinberg D, Vilageliu L.

Clin Genet. 2007 Mar;71(3):273-9.

PubMed [citation]

PMID:: 17309651

See all PubMed Citations (8)

Details of each submission

From OMIM, SCV000021145.3

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

Description

In 2 sibs from northeast Italy with infantile GM1-gangliosidosis with cardiac involvement (see 230500), Morrone et al. (2000) identified a homozygous 176G-A transition in exon 2 of the GLB1 gene, resulting in an arg59-to-his (R59H) substitution within the region common to the lysosomal enzyme and the EPB. In addition to classic type I symptoms, the patients showed dilated cardiomyopathy and hypertrophic cardiomyopathy, respectively .

Santamaria et al. (2007) identified the R59H mutation in 6 (15.8%) of 38 mutant GLB1 alleles in patients with GM1-gangliosidosis from South America, mainly Argentina. All had the type I phenotype (GM1G1; 230500). Two unrelated patients of Gypsy origin were homozygous for this mutation. Some, but apparently not all, had cardiac involvement.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Counsyl, SCV001132205.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneReviews, SCV001821206.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

High prevalence in Roma and Brazilian populations; associated with GM1 infantile and juvenile forms

#	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 Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein, SCV002512229.1

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

Description

ACMG classification criteria: PS3 supporting, PS4 strong, PM2 moderate, PM3 very strong, PP3 supporting, PP4 supporting

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From MGZ Medical Genetics Center, SCV002579350.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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