NM_014585.6(SLC40A1):c.744G>T (p.Gln248His) AND Hemochromatosis type 4

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

Germline classification:: Benign/Likely benign (2 submissions)
Last evaluated:: Oct 25, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000467098.12

Allele description

NM_014585.6(SLC40A1):c.744G>T (p.Gln248His)

Gene:

SLC40A1:solute carrier family 40 member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q32.2

Genomic location:

Preferred name:

NM_014585.6(SLC40A1):c.744G>T (p.Gln248His)

HGVS:

NC_000002.12:g.189565370C>A
NG_009027.1:g.20442G>T
NM_014585.6:c.744G>TMANE SELECT
NP_055400.1:p.Gln248His
NP_055400.1:p.Gln248His
LRG_837t1:c.744G>T
LRG_837:g.20442G>T
LRG_837p1:p.Gln248His
NC_000002.11:g.190430096C>A
NM_014585.5:c.744G>T
Q9NP59:p.Gln248His

Protein change:

Q248H

Links:

UniProtKB: Q9NP59#VAR_020295; dbSNP: rs11568350

Molecular consequence:

NM_014585.6:c.744G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hemochromatosis type 4 (HFE4)
Synonyms:: Hemochromatosis, autosomal dominant; Hemochromatosis due to defect in ferroportin
Identifiers:: MONDO: MONDO:0011631; MedGen: C1853733; Orphanet: 139491; OMIM: 606069

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000425693	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Likely benign (Feb 13, 2018)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 17490902, 23065513, 19150361, 15692071, 15831700, 16440176, 20460119, 17276706, 14636642, 21231898 Citation Link,
SCV000557073	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Oct 25, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000425693

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Likely benign
(Feb 13, 2018)

germline

clinical testing

PubMed (10)
[See all records that cite these PMIDs]

Citation Link,

SCV000557073

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Benign
(Oct 25, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

SLC40A1 Q248H allele frequencies and Q248H-associated risk of non-HFE iron overload in persons of sub-Saharan African descent.

Barton JC, Acton RT, Lee PL, West C.

Blood Cells Mol Dis. 2007 Sep-Oct;39(2):206-11. Epub 2007 May 9.

PubMed [citation]

PMID:: 17490902
PMCID:: PMC1986732

Reduced sensitivity of the ferroportin Q248H mutant to physiological concentrations of hepcidin.

Nekhai S, Xu M, Foster A, Kasvosve I, Diaz S, Machado RF, Castro OL, Kato GJ, Taylor JG 6th, Gordeuk VR.

Haematologica. 2013 Mar;98(3):455-63. doi: 10.3324/haematol.2012.066530. Epub 2012 Oct 12.

PubMed [citation]

PMID:: 23065513
PMCID:: PMC3659936

See all PubMed Citations (11)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000425693.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

#	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

From Invitae, SCV000557073.8

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

#	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 4, 2023

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