NM_000410.4(HFE):c.766G>A (p.Val256Ile) AND Hereditary hemochromatosis

Germline classification:: Uncertain significance (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:: RCV000549604.13

Allele description [Variation Report for NM_000410.4(HFE):c.766G>A (p.Val256Ile)]

NM_000410.4(HFE):c.766G>A (p.Val256Ile)

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.766G>A (p.Val256Ile)

HGVS:

NC_000006.12:g.26092834G>A
NG_008720.2:g.10554G>A
NM_000410.4:c.766G>AMANE SELECT
NM_001300749.3:c.766G>A
NM_001384164.1:c.766G>A
NM_001406751.1:c.757G>A
NM_001406752.1:c.502G>A
NM_139003.3:c.448G>A
NM_139004.3:c.490G>A
NM_139006.3:c.724G>A
NM_139007.3:c.502G>A
NM_139008.3:c.460G>A
NM_139009.3:c.697G>A
NM_139010.3:c.226G>A
NM_139011.3:c.77-285G>A
NP_000401.1:p.Val256Ile
NP_000401.1:p.Val256Ile
NP_001287678.1:p.Val256Ile
NP_001287678.1:p.Val256Ile
NP_001371093.1:p.Val256Ile
NP_001393680.1:p.Val253Ile
NP_001393681.1:p.Val168Ile
NP_620572.1:p.Val150Ile
NP_620573.1:p.Val164Ile
NP_620575.1:p.Val242Ile
NP_620576.1:p.Val168Ile
NP_620577.1:p.Val154Ile
NP_620578.1:p.Val233Ile
NP_620579.1:p.Val76Ile
LRG_748t1:c.766G>A
LRG_748:g.10554G>A
LRG_748p1:p.Val256Ile
NC_000006.11:g.26093062G>A
NM_000410.3:c.766G>A
NM_001300749.2:c.766G>A

Protein change:

V150I

Links:

dbSNP: rs202068193

NCBI 1000 Genomes Browser:

rs202068193

Molecular consequence:

NM_139011.3:c.77-285G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000410.4:c.766G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001300749.3:c.766G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001384164.1:c.766G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406751.1:c.757G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406752.1:c.502G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_139003.3:c.448G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_139004.3:c.490G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_139006.3:c.724G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_139007.3:c.502G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_139008.3:c.460G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_139009.3:c.697G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_139010.3:c.226G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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
SCV000633735	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 27, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21411349, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000633735

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 27, 2021)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Hereditary hemochromatosis: mutations in genes involved in iron homeostasis in Brazilian patients.

Santos PC, Cançado RD, Pereira AC, Schettert IT, Soares RA, Pagliusi RA, Hirata RD, Hirata MH, Teixeira AC, Figueiredo MS, Chiattone CS, Krieger JE, Guerra-Shinohara EM.

Blood Cells Mol Dis. 2011 Apr 15;46(4):302-7. doi: 10.1016/j.bcmd.2011.02.008.

PubMed [citation]

PMID:: 21411349

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000633735.3

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

Description

This sequence change replaces valine with isoleucine at codon 256 of the HFE protein (p.Val256Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs202068193, ExAC 0.01%). This missense change has been observed in individual(s) with hemochromatosis (PMID: 21411349). ClinVar contains an entry for this variant (Variation ID: 461194). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Nov 10, 2024

ClinVar

Relating variation to medicine