NM_000410.4(HFE):c.688TAC[1] (p.Tyr231del) AND Hemochromatosis type 1

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 27, 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:: RCV001582388.3

Allele description [Variation Report for NM_000410.4(HFE):c.688TAC[1] (p.Tyr231del)]

NM_000410.4(HFE):c.688TAC[1] (p.Tyr231del)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

6p22.2

Genomic location:

Preferred name:

NM_000410.4(HFE):c.688TAC[1] (p.Tyr231del)

HGVS:

NC_000006.12:g.26092756TAC[1]
NG_008720.2:g.10476TAC[1]
NM_000410.4:c.688TAC[1]MANE SELECT
NM_001300749.3:c.688_690TAC[1]
NM_001384164.1:c.688TAC[1]
NM_001406751.1:c.679_681TAC[1]
NM_001406752.1:c.424_426TAC[1]
NM_139003.3:c.370TAC[1]
NM_139004.3:c.412TAC[1]
NM_139006.3:c.646TAC[1]
NM_139007.3:c.424TAC[1]
NM_139008.3:c.382TAC[1]
NM_139009.3:c.619TAC[1]
NM_139010.3:c.148TAC[1]
NM_139011.3:c.77-360_77-358del
NP_000401.1:p.Tyr231del
NP_000401.1:p.Tyr231del
NP_001287678.1:p.Tyr231del
NP_001287678.1:p.Tyr231del
NP_001371093.1:p.Tyr231del
NP_001393680.1:p.Tyr228del
NP_001393681.1:p.Tyr143del
NP_620572.1:p.Tyr125del
NP_620573.1:p.Tyr139del
NP_620575.1:p.Tyr217del
NP_620576.1:p.Tyr143del
NP_620577.1:p.Tyr129del
NP_620578.1:p.Tyr208del
NP_620579.1:p.Tyr51del
LRG_748t1:c.688_690TAC[1]
LRG_748:g.10476TAC[1]
LRG_748p1:p.Tyr231del
NC_000006.11:g.26092984TAC[1]
NM_000410.3:c.688_690TAC[1]
NM_000410.3:c.691_693delTAC
NM_001300749.2:c.688TAC[1]

Protein change:

Y125del

Links:

dbSNP: rs766992720

NCBI 1000 Genomes Browser:

rs766992720

Molecular consequence:

NM_000410.4:c.688TAC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001384164.1:c.688TAC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_139003.3:c.370TAC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_139004.3:c.412TAC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_139006.3:c.646TAC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_139007.3:c.424TAC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_139008.3:c.382TAC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_139009.3:c.619TAC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_139010.3:c.148TAC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001300749.3:c.688_690TAC[1] - inframe_indel - [Sequence Ontology: SO:0001820]
NM_001406751.1:c.679_681TAC[1] - inframe_indel - [Sequence Ontology: SO:0001820]
NM_001406752.1:c.424_426TAC[1] - inframe_indel - [Sequence Ontology: SO:0001820]
NM_139011.3:c.77-360_77-358del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001821400	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Aug 27, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 29295803, 22093335, 20017200 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001821400

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Aug 27, 2021)

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

Differential effects on sodium current impairments by distinct SCN1A mutations in GABAergic neurons derived from Dravet syndrome patients.

Kim HW, Quan Z, Kim YB, Cheong E, Kim HD, Cho M, Jang J, Yoo YR, Lee JS, Kim JH, Kim YI, Kim DS, Kang HC.

Brain Dev. 2018 Apr;40(4):287-298. doi: 10.1016/j.braindev.2017.12.002. Epub 2017 Dec 30.

PubMed [citation]

PMID:: 29295803

A novel Y231del mutation of HFE in hereditary haemochromatosis provides in vivo evidence that the Huh-7 is a human haemochromatotic cell line.

Takano A, Niimi H, Atarashi Y, Sawasaki T, Terasaki T, Nakabayashi T, Kitajima I, Tobe K, Takahara T.

Liver Int. 2011 Nov;31(10):1593-7. doi: 10.1111/j.1478-3231.2011.02620.x. Epub 2011 Aug 17.

PubMed [citation]

PMID:: 22093335

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001821400.1

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

Description

Variant summary: HFE c.691_693delTAC (p.Tyr231del) results in an in-frame deletion that is predicted to remove 1 amino acid from the encoded protein. The variant allele was found at a frequency of 3.6e-05 in 251484 control chromosomes (gnomAD). c.691_693delTAC has been reported in the literature in a 43-year-old homozygous man who was diagnosed as having Hereditary haemochromatosis. His 42-year-old sister who was also homozygous for the variant, had no clinical symptoms at the time of the examination; she was noted however with suggested presence of a slight iron accumulation in the liver (Takano_2011). These data indicate that the variant may be associated with disease. Experimental evidence evaluating an impact on protein function demonstrated the variant leads to defective HFE traffic to the cell surface and was associated with inadequate hepcidin expression (Vecchi_2010). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely 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: Mar 30, 2024

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