NM_000147.5(FUCA1):c.1229T>G (p.Leu410Arg) AND Fucosidosis

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

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: May 17, 2023
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:: RCV000000727.4

Allele description

NM_000147.5(FUCA1):c.1229T>G (p.Leu410Arg)

Gene:

FUCA1:alpha-L-fucosidase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.11

Genomic location:

Preferred name:

NM_000147.5(FUCA1):c.1229T>G (p.Leu410Arg)

Other names:

FUCA1, LEU405ARG

HGVS:

NC_000001.11:g.23846105A>C
NG_013346.1:g.27265T>G
NM_000147.5:c.1229T>GMANE SELECT
NP_000138.2:p.Leu410Arg
NC_000001.10:g.24172595A>C
P04066:p.Leu410Arg

Protein change:

L410R

Links:

UniProtKB: P04066#VAR_016235; OMIM: 612280.0012; dbSNP: rs80358199

NCBI 1000 Genomes Browser:

rs80358199

Molecular consequence:

NM_000147.5:c.1229T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Fucosidosis
Synonyms:: Alpha-l-fucosidase deficiency; Lysosomal storage disease caused by defective alpha-L-fucosidase with accumulation of fucose in the tissues
Identifiers:: MONDO: MONDO:0009254; MedGen: C0016788; Orphanet: 349; OMIM: 230000

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000020877	OMIM	no assertion criteria provided	Pathogenic (Aug 1, 1998)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 9762612, 1214294
SCV004291764	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (May 17, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 9762612, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000020877

OMIM

no assertion criteria provided

Pathogenic
(Aug 1, 1998)

germline

literature only

PubMed (2)
[See all records that cite these PMIDs]

SCV004291764

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(May 17, 2023)

germline

clinical testing

PubMed (2)
[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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A note on fucosidosis in a mentally subnormal female.

Primrose DA.

J Ment Defic Res. 1975 Sep-Dec;19(3-4):267. No abstract available.

PubMed [citation]

PMID:: 1214294

A fucosidosis patient with relative longevity and a missense mutation in exon 7 of the alpha-fucosidase gene.

Fleming CJ, Sinclair DU, White EJ, Winchester B, Whiteford ML, Connor JM.

J Inherit Metab Dis. 1998 Aug;21(6):688-9. No abstract available.

PubMed [citation]

PMID:: 9762612

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000020877.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

Fleming et al. (1998) described a leu405-to-arg (L405R) mutation in the FUCA1 gene in homozygous state in a patient with fucosidosis (230000) who was 46 years old the time of review in 1997. This was said to be the first report of a patient with fucosidosis living into the fifth decade. The substituted amino acid is conserved in 4 species. The residual activity of alpha-fucosidase was less than 1% and no cross-reacting material was identified in the patient's fibroblasts. The patient had previously been described by Primrose (1975).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV004291764.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

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. 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 FUCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 692). This variant is also known as L405R. This missense change has been observed in individual(s) with fucosidosis (PMID: 9762612). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 410 of the FUCA1 protein (p.Leu410Arg).

#	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: Feb 20, 2024

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