NM_000157.4(GBA1):c.1604G>A (p.Arg535His) AND not specified

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 23, 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:: RCV004018560.1

Allele description [Variation Report for NM_000157.4(GBA1):c.1604G>A (p.Arg535His)]

NM_000157.4(GBA1):c.1604G>A (p.Arg535His)

Genes:

LOC106627981:GBA recombination region [Gene]
GBA1:glucosylceramidase beta 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q22

Genomic location:

Preferred name:

NM_000157.4(GBA1):c.1604G>A (p.Arg535His)

Other names:

R496H

HGVS:

NC_000001.11:g.155235002C>T
NG_009783.1:g.14696G>A
NG_042867.1:g.1464C>T
NM_000157.3(GBA):c.1604G>A
NM_000157.4:c.1604G>AMANE SELECT
NM_001005741.3:c.1604G>A
NM_001005742.3:c.1604G>A
NM_001171811.2:c.1343G>A
NM_001171812.2:c.1457G>A
NP_000148.2:p.Arg535His
NP_001005741.1:p.Arg535His
NP_001005742.1:p.Arg535His
NP_001165282.1:p.Arg448His
NP_001165283.1:p.Arg486His
NC_000001.10:g.155204793C>T
NM_000157.2:c.1604G>A
NM_000157.3(GBA):c.1604G>A
NM_000157.3:c.1604G>A
NM_000157.4:c.1604G>A
NM_001005741.2:c.1604G>A
NM_001005741.3:c.1604G>A
NM_001005742.2:c.1604G>A
P04062:p.Arg535His
c.1604G>A (p.Arg535His)

Protein change:

R448H; ARG496HIS

Links:

UniProtKB: P04062#VAR_003328; OMIM: 606463.0022; dbSNP: rs75822236

NCBI 1000 Genomes Browser:

rs75822236

Molecular consequence:

NM_000157.4:c.1604G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001005741.3:c.1604G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001005742.3:c.1604G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001171811.2:c.1343G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001171812.2:c.1457G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002755628	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jun 23, 2022)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 12972024, 1487244, 16293621, 17427031, 20672374, 23430543, 23588557, 23699752, 27735925, 8432537 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002755628

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jun 23, 2022)

germline

clinical testing

PubMed (10)
[See all records that cite these PMIDs]

Citation Link

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	clinical testing

Citations

PubMed

The 1604A (R496H) mutation in Gaucher disease: genotype/phenotype correlation.

Brautbar A, Elstein D, Abrahamov A, Zeigler M, Chicco G, Beutler E, Scott CR, Zimran A.

Blood Cells Mol Dis. 2003 Sep-Oct;31(2):187-9; discussion 190-1.

PubMed [citation]

PMID:: 12972024

Rapid identification of mutations in the glucocerebrosidase gene of Gaucher disease patients by analysis of single-strand conformation polymorphisms.

Kawame H, Hasegawa Y, Eto Y, Maekawa K.

Hum Genet. 1992 Nov;90(3):294-6.

PubMed [citation]

PMID:: 1487244

See all PubMed Citations (10)

Details of each submission

From Ambry Genetics, SCV002755628.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

Description

The p.R535H pathogenic mutation (also known as c.1604G>A and p.R496H), located in coding exon 11 of the GBA gene, results from a G to A substitution at nucleotide position 1604. The arginine at codon 535 is replaced by histidine, an amino acid with highly similar properties. In one study of 2,012 individuals screened for various autosomal recessive conditions, it was the third most common GBA alteration detected with a carrier frequency of 1 in 335 (Scott SA et al. Hum. Mutat. 2010; 31(11):1240-50). In addition, this variant has been detected on several alleles from individuals with Gaucher disease; however, specific phenotype information and/or additional mutation and phase information was not provided (Beutler E et al. Genomics 1993;15(1):203-5; Siebert M et al. JIMD Rep 2013 ; 9():7-16; Alfonso P et al. J. Hum. Genet. 2007; 52(5):391-6). This variant has also been detected in two individuals with Parkinson disease and Lewy body dementia (Chahine LM et al. JAMA Neurol 2013; 70(7):852-8; Nalls MA et al. JAMA Neurol 2013 ; 70(6):727-35). In another study which characterized basic kinetic, stability, and activator response properties of this alteration in an in vitro environment, authors concluded that this alteration has little, if any, in vitro catalytic activity (Liou B et al. J. Biol. Chem. 2006; 281(7):4242-53). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#	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: Sep 8, 2024

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