NM_000404.4(GLB1):c.1768C>T (p.Arg590Cys) AND Infantile GM1 gangliosidosis

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 1, 2017
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:: RCV000175003.4

Allele description [Variation Report for NM_000404.4(GLB1):c.1768C>T (p.Arg590Cys)]

NM_000404.4(GLB1):c.1768C>T (p.Arg590Cys)

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.1768C>T (p.Arg590Cys)

Other names:

p.Arg590Cys

HGVS:

NC_000003.12:g.32997311G>A
NG_009005.1:g.104892C>T
NM_000404.4:c.1768C>TMANE SELECT
NM_001079811.3:c.1678C>T
NM_001135602.3:c.1375C>T
NM_001317040.2:c.1912C>T
NM_001393580.1:c.1734+16745C>T
NP_000395.3:p.Arg590Cys
NP_001073279.2:p.Arg560Cys
NP_001129074.2:p.Arg459Cys
NP_001303969.2:p.Arg638Cys
NC_000003.11:g.33038803G>A
NM_000404.2:c.1768C>T
NM_000404.3:c.1768C>T

Protein change:

R459C

Links:

dbSNP: rs794727165

NCBI 1000 Genomes Browser:

rs794727165

Molecular consequence:

NM_001393580.1:c.1734+16745C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000404.4:c.1768C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001079811.3:c.1678C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001135602.3:c.1375C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001317040.2:c.1912C>T - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

Unknown function

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
SCV000807609	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 1, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16941474, 25741868, 25326635
SCV002822858	Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000807609

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Sep 1, 2017)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV002822858

Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

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	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Twenty-one novel mutations in the GLB1 gene identified in a large group of GM1-gangliosidosis and Morquio B patients: possible common origin for the prevalent p.R59H mutation among gypsies.

Santamaria R, Chabás A, Coll MJ, Miranda CS, Vilageliu L, Grinberg D.

Hum Mutat. 2006 Oct;27(10):1060.

PubMed [citation]

PMID:: 16941474

Molecular findings among patients referred for clinical whole-exome sequencing.

Yang Y, Muzny DM, Xia F, Niu Z, Person R, Ding Y, Ward P, Braxton A, Wang M, Buhay C, Veeraraghavan N, Hawes A, Chiang T, Leduc M, Beuten J, Zhang J, He W, Scull J, Willis A, Landsverk M, Craigen WJ, Bekheirnia MR, et al.

JAMA. 2014 Nov 12;312(18):1870-9. doi: 10.1001/jama.2014.14601.

PubMed [citation]

PMID:: 25326635
PMCID:: PMC4326249

See all PubMed Citations (3)

Details of each submission

From Baylor Genetics, SCV000807609.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing (GTR000508680.4)	PubMed (3)

Description

This mutation has been previously reported as disease-causing and was found once in our laboratory homozygous in a 6-month-old male with motor delays, hypotonia, plagiocephaly, dilated aortic root, partial pulmonary venous connection, pectus, club foot, hepatomegaly, T cell lymphopenia. Heterozygotes are expected to be asymptomatic carriers.

#	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	(GTR000508680.4)	not provided	not provided	not provided	not provided

From Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics, SCV002822858.1

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

Description

The homozygous missense variation in exon 16 of GLB1 gene that results in the amino acid substitution to cysteine for arginine at codon of 590 was detected. The variant c.1768C>T (p.Arg590Cys) has not been reported in 1000 genome and has a MAF of 0.0012% in the gnomAD database. The insilico prediction of the variant is dIsease causing by LRT, MutPred, PROVEAN and SIFT

#	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: Sep 29, 2024

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