NM_000157.4(GBA1):c.706C>T (p.Leu236Phe) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 31, 2021
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:: RCV001193937.2

Allele description [Variation Report for NM_000157.4(GBA1):c.706C>T (p.Leu236Phe)]

NM_000157.4(GBA1):c.706C>T (p.Leu236Phe)

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.706C>T (p.Leu236Phe)

HGVS:

NC_000001.11:g.155238189G>A
NG_009783.1:g.11509C>T
NG_042867.1:g.4651G>A
NM_000157.4:c.706C>TMANE SELECT
NM_001005741.3:c.706C>T
NM_001005742.3:c.706C>T
NM_001171811.2:c.445C>T
NM_001171812.2:c.559C>T
NP_000148.2:p.Leu236Phe
NP_001005741.1:p.Leu236Phe
NP_001005742.1:p.Leu236Phe
NP_001165282.1:p.Leu149Phe
NP_001165283.1:p.Leu187Phe
NC_000001.10:g.155207980G>A
NM_001005741.2:c.706C>T

Protein change:

L149F

Links:

dbSNP: rs1671865905

NCBI 1000 Genomes Browser:

rs1671865905

Molecular consequence:

NM_000157.4:c.706C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001005741.3:c.706C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001005742.3:c.706C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001171811.2:c.445C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001171812.2:c.559C>T - 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
SCV001363115	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Mar 31, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16185900, 19790257, 21856586, 32623306 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001363115

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Mar 31, 2021)

germline

clinical testing

PubMed (4)
[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

Hematologically important mutations: Gaucher disease.

Beutler E, Gelbart T, Scott CR.

Blood Cells Mol Dis. 2005 Nov-Dec;35(3):355-64. Epub 2005 Sep 26. Review. No abstract available.

PubMed [citation]

PMID:: 16185900

Structural aspects of therapeutic enzymes to treat metabolic disorders.

Kang TS, Stevens RC.

Hum Mutat. 2009 Dec;30(12):1591-610. doi: 10.1002/humu.21111. Review.

PubMed [citation]

PMID:: 19790257

See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001363115.2

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

Description

Variant summary: GBA c.706C>T (p.Leu236Phe) results in a non-conservative amino acid change located in the Glycosyl hydrolase family 30, TIM-barrel domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251472 control chromosomes. c.706C>T has been reported in the literature in a individuals indicated to have severe Gaucher Disease (Beutler_2006) and Parkinson's Disease (Boreau_2011) without second allele specified. These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. However, another missense change at this codon, L236P and nearby codons, G234E, G234W, S235P, L236P, K237E, K237T, have been reported in association with Gaucher disease (via HGMD), therefore, suggesting the region is important for protein function. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

#	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: Mar 4, 2023

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