NM_000404.4(GLB1):c.1643T>A (p.Leu548His) AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 18, 2022
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:: RCV001948764.4

Allele description

NM_000404.4(GLB1):c.1643T>A (p.Leu548His)

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.1643T>A (p.Leu548His)

HGVS:

NC_000003.12:g.33014147A>T
NG_009005.1:g.88056T>A
NM_000404.4:c.1643T>AMANE SELECT
NM_001079811.3:c.1553T>A
NM_001135602.3:c.1250T>A
NM_001317040.2:c.1787T>A
NM_001393580.1:c.1643T>A
NP_000395.3:p.Leu548His
NP_001073279.2:p.Leu518His
NP_001129074.2:p.Leu417His
NP_001303969.2:p.Leu596His
NP_001380509.1:p.Leu548His
NC_000003.11:g.33055639A>T

Protein change:

L417H

Links:

dbSNP: rs1335107953

NCBI 1000 Genomes Browser:

rs1335107953

Molecular consequence:

NM_000404.4:c.1643T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001079811.3:c.1553T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001135602.3:c.1250T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001317040.2:c.1787T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001393580.1:c.1643T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Mucopolysaccharidosis, MPS-IV-B (MPS4B)
Synonyms:: MPS IVB; Morquio syndrome B; MPS 4B; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009660; MedGen: C0086652; Orphanet: 582; OMIM: 253010

Name:: GM1 gangliosidosis
Synonyms:: Beta galactosidase 1 deficiency; GLB 1 deficiency
Identifiers:: MONDO: MONDO:0018149; MedGen: C0085131

Recent activity

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noelin-2 isoform 2 precursor [Homo sapiens]
noelin-2 isoform 2 precursor [Homo sapiens]
gi|17157993|ref|NP_477512.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002211106	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 18, 2022)	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

SCV002211106

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 18, 2022)

germline

clinical testing

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

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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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002211106.2

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

Description

This sequence change replaces leucine, which is neutral and non-polar, with histidine, which is basic and polar, at codon 548 of the GLB1 protein (p.Leu548His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GLB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1437570). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GLB1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Dec 24, 2023

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