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NM_000410.4(HFE):c.502G>T (p.Glu168Ter) AND Hereditary hemochromatosis

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 29, 2022
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:
RCV001058987.14

Allele description [Variation Report for NM_000410.4(HFE):c.502G>T (p.Glu168Ter)]

NM_000410.4(HFE):c.502G>T (p.Glu168Ter)

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.502G>T (p.Glu168Ter)
HGVS:
  • NC_000006.12:g.26091475G>T
  • NG_008720.2:g.9195G>T
  • NM_000410.4:c.502G>TMANE SELECT
  • NM_001300749.3:c.502G>T
  • NM_001384164.1:c.502G>T
  • NM_001406751.1:c.502G>T
  • NM_001406752.1:c.238G>T
  • NM_139003.3:c.340+371G>T
  • NM_139004.3:c.340+371G>T
  • NM_139006.3:c.502G>T
  • NM_139007.3:c.238G>T
  • NM_139008.3:c.238G>T
  • NM_139009.3:c.433G>T
  • NM_139010.3:c.77-1210G>T
  • NM_139011.3:c.77-1644G>T
  • NP_000401.1:p.Glu168Ter
  • NP_000401.1:p.Glu168Ter
  • NP_001287678.1:p.Glu168Ter
  • NP_001287678.1:p.Glu168Ter
  • NP_001371093.1:p.Glu168Ter
  • NP_001393680.1:p.Glu168Ter
  • NP_001393681.1:p.Glu80Ter
  • NP_620575.1:p.Glu168Ter
  • NP_620576.1:p.Glu80Ter
  • NP_620577.1:p.Glu80Ter
  • NP_620578.1:p.Glu145Ter
  • LRG_748t1:c.502G>T
  • LRG_748:g.9195G>T
  • LRG_748p1:p.Glu168Ter
  • NC_000006.11:g.26091703G>T
  • NM_000410.3:c.502G>T
  • NM_001300749.2:c.502G>T
Protein change:
E145*
Links:
dbSNP: rs146519482
NCBI 1000 Genomes Browser:
rs146519482
Molecular consequence:
  • NM_139003.3:c.340+371G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_139004.3:c.340+371G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_139010.3:c.77-1210G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_139011.3:c.77-1644G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000410.4:c.502G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001300749.3:c.502G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001384164.1:c.502G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406751.1:c.502G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406752.1:c.238G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_139006.3:c.502G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_139007.3:c.238G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_139008.3:c.238G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_139009.3:c.433G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001223590Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Dec 29, 2022) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Two novel nonsense mutations of HFE gene in five unrelated italian patients with hemochromatosis.

Piperno A, Arosio C, Fossati L, Viganò M, Trombini P, Vergani A, Mancia G.

Gastroenterology. 2000 Aug;119(2):441-5.

PubMed [citation]
PMID:
10930379

Rare HFE variants are the most frequent cause of hemochromatosis in non-c282y homozygous patients with hemochromatosis.

Hamdi-Rozé H, Beaumont-Epinette MP, Ben Ali Z, Le Lan C, Loustaud-Ratti V, Causse X, Loreal O, Deugnier Y, Brissot P, Jouanolle AM, Bardou-Jacquet E.

Am J Hematol. 2016 Dec;91(12):1202-1205. doi: 10.1002/ajh.24535. Epub 2016 Aug 22.

PubMed [citation]
PMID:
27518069
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001223590.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 88946). This premature translational stop signal has been observed in individuals with hemochromatosis (PMID: 10930379). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu168*) in the HFE gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HFE are known to be pathogenic (PMID: 27518069).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 3, 2024