NM_000410.4(HFE):c.829G>A (p.Glu277Lys) AND Hemochromatosis type 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 3, 2016
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:: RCV000473336.7

Allele description [Variation Report for NM_000410.4(HFE):c.829G>A (p.Glu277Lys)]

NM_000410.4(HFE):c.829G>A (p.Glu277Lys)

Gene:

HFE:homeostatic iron regulator [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p22.2

Genomic location:

Preferred name:

NM_000410.4(HFE):c.829G>A (p.Glu277Lys)

HGVS:

NC_000006.12:g.26092897G>A
NG_008720.2:g.10617G>A
NM_000410.4:c.829G>AMANE SELECT
NM_001300749.3:c.829G>A
NM_001384164.1:c.829G>A
NM_001406751.1:c.820G>A
NM_001406752.1:c.565G>A
NM_139003.3:c.511G>A
NM_139004.3:c.553G>A
NM_139006.3:c.787G>A
NM_139007.3:c.565G>A
NM_139008.3:c.523G>A
NM_139009.3:c.760G>A
NM_139010.3:c.289G>A
NM_139011.3:c.77-222G>A
NP_000401.1:p.Glu277Lys
NP_000401.1:p.Glu277Lys
NP_001287678.1:p.Glu277Lys
NP_001287678.1:p.Glu277Lys
NP_001371093.1:p.Glu277Lys
NP_001393680.1:p.Glu274Lys
NP_001393681.1:p.Glu189Lys
NP_620572.1:p.Glu171Lys
NP_620573.1:p.Glu185Lys
NP_620575.1:p.Glu263Lys
NP_620576.1:p.Glu189Lys
NP_620577.1:p.Glu175Lys
NP_620578.1:p.Glu254Lys
NP_620579.1:p.Glu97Lys
LRG_748t1:c.829G>A
LRG_748:g.10617G>A
LRG_748p1:p.Glu277Lys
NC_000006.11:g.26093125G>A
NM_000410.3:c.829G>A
NM_001300749.2:c.829G>A
Q30201:p.Glu277Lys

Protein change:

E171K

Links:

UniProtKB: Q30201#VAR_008731; dbSNP: rs140080192

NCBI 1000 Genomes Browser:

rs140080192

Molecular consequence:

NM_139011.3:c.77-222G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000410.4:c.829G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001300749.3:c.829G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001384164.1:c.829G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406751.1:c.820G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406752.1:c.565G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_139003.3:c.511G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_139004.3:c.553G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_139006.3:c.787G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_139007.3:c.565G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_139008.3:c.523G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_139009.3:c.760G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_139010.3:c.289G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hemochromatosis type 1 (HFE1)
Synonyms:: HFE-Associated Hereditary Hemochromatosis
Identifiers:: MONDO: MONDO:0021001; MedGen: C3469186; OMIM: 235200

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000461886	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 09 May 2019)	Uncertain significance (Aug 3, 2016)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10612845, 22624560, 18762941 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000461886

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 09 May 2019)

Uncertain significance
(Aug 3, 2016)

germline

clinical testing

PubMed (3)
[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

Two novel polymorphisms (E277K and V212V) in the haemochromatosis gene HFE.

Bradbury R, Fagan E, Payne SJ.

Hum Mutat. 2000 Jan;15(1):120. No abstract available.

PubMed [citation]

PMID:: 10612845

The functional significance of E277K and V295A HFE mutations.

Silva B, Martins R, Proença D, Fleming R, Faustino P.

Br J Haematol. 2012 Aug;158(3):399-408. doi: 10.1111/j.1365-2141.2012.09164.x. Epub 2012 May 25.

PubMed [citation]

PMID:: 22624560

See all PubMed Citations (3)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000461886.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The HFE c.829G>A (p.Glu277Lys) variant is a missense variant that has been reported in at least one study, in which it was found in a compound heterozygous state with a second missense variant in one Portuguese individual with suspected hereditary hemochromatosis (Mendes et al. 2009). Family studies showed that the individual's brother had the same genotype and high serum ferritin levels. Functional studies by Silva et al. (2012) suggest that the p.Glu277Lys variant affects splicing, protein cell surface presentation and protein processing. The p.Glu277Lys variant was absent from 50 controls (Bradbury et al. 2000) and is reported at a frequency of 0.02459 in the South Asian population of the Exome Aggregation Consortium. This allele frequency is high but is consistent with the disease prevalence, reduced penetrance and mild phenotype. The evidence for this variant is limited. The p.Glu277Lys variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for hereditary hemochromatosis. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

#	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: Oct 20, 2024

ClinVar

Relating variation to medicine