NM_000169.3(GLA):c.812G>T (p.Gly271Val) AND Fabry disease

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 16, 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:: RCV002013540.7

Allele description [Variation Report for NM_000169.3(GLA):c.812G>T (p.Gly271Val)]

NM_000169.3(GLA):c.812G>T (p.Gly271Val)

Genes:

RPL36A-HNRNPH2:RPL36A-HNRNPH2 readthrough [Gene - HGNC]
GLA:galactosidase alpha [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq22.1

Genomic location:

Preferred name:

NM_000169.3(GLA):c.812G>T (p.Gly271Val)

HGVS:

NC_000023.11:g.101398557C>A
NG_007119.1:g.14407G>T
NM_000169.3:c.812G>TMANE SELECT
NM_001199973.2:c.300+3100C>A
NM_001199974.2:c.177+6735C>A
NM_001406747.1:c.935G>T
NM_001406748.1:c.812G>T
NP_000160.1:p.Gly271Val
NP_000160.1:p.Gly271Val
NP_001393676.1:p.Gly312Val
NP_001393677.1:p.Gly271Val
LRG_672t1:c.812G>T
LRG_672:g.14407G>T
LRG_672p1:p.Gly271Val
NC_000023.10:g.100653545C>A
NM_000169.2:c.812G>T
NR_164783.1:n.891G>T
NR_176252.1:n.742G>T
NR_176253.1:n.949G>T

Protein change:

G271V

Links:

dbSNP: rs869312429

NCBI 1000 Genomes Browser:

rs869312429

Molecular consequence:

NM_001199973.2:c.300+3100C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001199974.2:c.177+6735C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000169.3:c.812G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406747.1:c.935G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406748.1:c.812G>T - missense variant - [Sequence Ontology: SO:0001583]
NR_164783.1:n.891G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176252.1:n.742G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176253.1:n.949G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Fabry disease
Synonyms:: Angiokeratoma, diffuse; Anderson-Fabry disease; Hereditary dystopic lipidosis; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010526; MedGen: C0002986; Orphanet: 324; OMIM: 301500; Human Phenotype Ontology: HP:0001071

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002288925	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Feb 16, 2021)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 30715505, 20498269, 29037082, 21598360, 16595074, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002288925

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Feb 16, 2021)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

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

Monogenic mimics of Behçet's disease in the young.

Papadopoulou C, Omoyinmi E, Standing A, Pain CE, Booth C, D'Arco F, Gilmour K, Buckland M, Eleftheriou D, Brogan PA.

Rheumatology (Oxford). 2019 Jul 1;58(7):1227-1238. doi: 10.1093/rheumatology/key445.

PubMed [citation]

PMID:: 30715505

Fabry disease mimicking hypertrophic cardiomyopathy: genetic screening needed for establishing the diagnosis in women.

Havndrup O, Christiansen M, Stoevring B, Jensen M, Hoffman-Bang J, Andersen PS, Hasholt L, Nørremølle A, Feldt-Rasmussen U, Køber L, Bundgaard H.

Eur J Heart Fail. 2010 Jun;12(6):535-40. doi: 10.1093/eurjhf/hfq073.

PubMed [citation]

PMID:: 20498269

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002288925.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Gly271 amino acid residue in GLA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16595074, 30715505, 20498269, 29037082). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this variant affects GLA protein function (PMID: 21598360). This variant has been observed in individual(s) with Fabry disease (PMID: 16595074). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with valine at codon 271 of the GLA protein (p.Gly271Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine.

#	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 29, 2024

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