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NM_000404.4(GLB1):c.808T>G (p.Tyr270Asp)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
7 (Most recent: Sep 2, 2021)
Last evaluated:
Oct 23, 2020
Accession:
VCV000284172.9
Variation ID:
284172
Description:
single nucleotide variant
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NM_000404.4(GLB1):c.808T>G (p.Tyr270Asp)

Allele ID
268409
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
3p22.3
Genomic location
3: 33051989 (GRCh38) GRCh38 UCSC
3: 33093481 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000003.12:g.33051989A>C
NG_009005.1:g.50214T>G
NM_000404.4:c.808T>G MANE Select NP_000395.3:p.Tyr270Asp missense
... more HGVS
Protein change
Y270D, Y318D, Y139D, Y240D
Other names
-
Canonical SPDI
NC_000003.12:33051988:A:C
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00002
The Genome Aggregation Database (gnomAD) 0.00006
Trans-Omics for Precision Medicine (TOPMed) 0.00002
The Genome Aggregation Database (gnomAD) 0.00001
Exome Aggregation Consortium (ExAC) 0.00002
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
Links
ClinGen: CA2299582
dbSNP: rs376663785
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 3 criteria provided, multiple submitters, no conflicts Oct 23, 2020 RCV000394616.5
Pathogenic 1 criteria provided, single submitter Apr 26, 2016 RCV000623067.1
Pathogenic 1 criteria provided, single submitter Aug 26, 2020 RCV000689244.3
Likely pathogenic 1 criteria provided, single submitter Apr 6, 2017 RCV000666452.1
Pathogenic 1 criteria provided, single submitter Feb 8, 2018 RCV000780303.1

Clinical features observed in individuals with this variant

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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
GLB1 - - GRCh38
GRCh37
466 508

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Oct 21, 2015)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000336686.4
Submitted: (Sep 19, 2018)
Evidence details
Publications
PubMed (1)
Other databases
http://www.egl-eurofins.com/emvc…
Likely pathogenic
(Apr 06, 2017)
criteria provided, single submitter
Method: clinical testing
Infantile GM1 gangliosidosis
GM1 gangliosidosis type 2
GM1 gangliosidosis type 3
Mucopolysaccharidosis, MPS-IV-B
Allele origin: unknown
Counsyl
Accession: SCV000790747.1
Submitted: (Jul 10, 2018)
Evidence details
Publications
PubMed (2)
Pathogenic
(Feb 08, 2018)
criteria provided, single submitter
Method: clinical testing
Mucopolysaccharidosis, MPS-IV-B
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000917465.1
Submitted: (Apr 24, 2019)
Evidence details
Publications
PubMed (2)
Comment:
Variant summary: GLB1 c.808T>G (p.Tyr270Asp) results in a non-conservative amino acid change located in the catalytic domain of the encoded protein sequence. Five of five … (more)
Pathogenic
(Apr 26, 2016)
criteria provided, single submitter
Method: clinical testing
Inborn genetic diseases
Allele origin: germline
Ambry Genetics
Accession: SCV000741501.2
Submitted: (Oct 09, 2020)
Evidence details
Pathogenic
(Oct 23, 2020)
criteria provided, single submitter
Method: clinical testing
not provided
(Autosomal recessive inheritance)
Allele origin: germline
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001447100.1
Submitted: (Oct 23, 2020)
Evidence details
Pathogenic
(Aug 26, 2020)
criteria provided, single submitter
Method: clinical testing
Mucopolysaccharidosis, MPS-IV-B
GM1 gangliosidosis
Allele origin: germline
Invitae
Accession: SCV000816886.3
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (4)
Comment:
This sequence change replaces tyrosine with aspartic acid at codon 270 of the GLB1 protein (p.Tyr270Asp). The tyrosine residue is highly conserved and there is … (more)
Pathogenic
(Aug 19, 2020)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV001826789.1
Submitted: (Sep 02, 2021)
Evidence details
Comment:
Published functional studies demonstrate a damaging effect: undetectable enzyme activity (Hofer et al., 2009; Higaki et al., 2011); Not observed at a significant frequency in … (more)

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Chemical chaperone therapy: chaperone effect on mutant enzyme and cellular pathophysiology in β-galactosidase deficiency. Higaki K Human mutation 2011 PMID: 21520340
GM1 gangliosidosis and Morquio B disease: expression analysis of missense mutations affecting the catalytic site of acid beta-galactosidase. Hofer D Human mutation 2009 PMID: 19472408
Mutation analyses in 17 patients with deficiency in acid beta-galactosidase: three novel point mutations and high correlation of mutation W273L with Morquio disease type B. Paschke E Human genetics 2001 PMID: 11511921
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=GLB1 - - - -

Text-mined citations for rs376663785...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 27, 2021