NM_000410.4(HFE):c.892G>T (p.Glu298Ter) AND Hereditary hemochromatosis

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

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 21, 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:: RCV002230773.13

Allele description

NM_000410.4(HFE):c.892G>T (p.Glu298Ter)

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.892G>T (p.Glu298Ter)

HGVS:

NC_000006.12:g.26092960G>T
NG_008720.2:g.10680G>T
NM_000410.4:c.892G>TMANE SELECT
NM_001300749.3:c.892G>T
NM_001384164.1:c.892G>T
NM_001406751.1:c.883G>T
NM_001406752.1:c.628G>T
NM_139003.3:c.574G>T
NM_139004.3:c.616G>T
NM_139006.3:c.850G>T
NM_139007.3:c.628G>T
NM_139008.3:c.586G>T
NM_139009.3:c.823G>T
NM_139010.3:c.352G>T
NM_139011.3:c.77-159G>T
NP_000401.1:p.Glu298Ter
NP_000401.1:p.Glu298Ter
NP_001287678.1:p.Glu298Ter
NP_001287678.1:p.Glu298Ter
NP_001371093.1:p.Glu298Ter
NP_001393680.1:p.Glu295Ter
NP_001393681.1:p.Glu210Ter
NP_620572.1:p.Glu192Ter
NP_620573.1:p.Glu206Ter
NP_620575.1:p.Glu284Ter
NP_620576.1:p.Glu210Ter
NP_620577.1:p.Glu196Ter
NP_620578.1:p.Glu275Ter
NP_620579.1:p.Glu118Ter
LRG_748t1:c.892G>T
LRG_748:g.10680G>T
LRG_748p1:p.Glu298Ter
NC_000006.11:g.26093188G>T
NM_000410.3:c.892G>T
NM_001300749.2:c.892G>T

Protein change:

E118*

Links:

dbSNP: rs749553271

NCBI 1000 Genomes Browser:

rs749553271

Molecular consequence:

NM_139011.3:c.77-159G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000410.4:c.892G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001300749.3:c.892G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001384164.1:c.892G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406751.1:c.883G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406752.1:c.628G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_139003.3:c.574G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_139004.3:c.616G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_139006.3:c.850G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_139007.3:c.628G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_139008.3:c.586G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_139009.3:c.823G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_139010.3:c.352G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hereditary hemochromatosis (HFE)
Identifiers:: MONDO: MONDO:0006507; MedGen: C0392514; OMIM: PS235200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000546054	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 21, 2016)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 9482913, 10557317, 10381492, 24920245, 10930379, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000546054

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 21, 2016)

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

HFE gene knockout produces mouse model of hereditary hemochromatosis.

Zhou XY, Tomatsu S, Fleming RE, Parkkila S, Waheed A, Jiang J, Fei Y, Brunt EM, Ruddy DA, Prass CE, Schatzman RC, O'Neill R, Britton RS, Bacon BR, Sly WS.

Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2492-7.

PubMed [citation]

PMID:: 9482913
PMCID:: PMC19387

Experimental hemochromatosis due to MHC class I HFE deficiency: immune status and iron metabolism.

Bahram S, Gilfillan S, Kühn LC, Moret R, Schulze JB, Lebeau A, Schümann K.

Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13312-7.

PubMed [citation]

PMID:: 10557317
PMCID:: PMC23944

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000546054.5

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

Description

While this particular variant has not been reported in the literature, truncating variants in HFE are known to contribute to hemochromatosis when homozygous or present with a second pathogenic allele in HFE (PMID: 9482913, 10557317, 10381492, 24920245, 10930379). This sequence change creates a premature translational stop signal at codon 298 (p.Glu298*) of the HFE gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as 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: Sep 16, 2024

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