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NM_014585.6(SLC40A1):c.190T>C (p.Tyr64His) AND Hemochromatosis type 4

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jul 16, 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:
RCV001228946.8

Allele description [Variation Report for NM_014585.6(SLC40A1):c.190T>C (p.Tyr64His)]

NM_014585.6(SLC40A1):c.190T>C (p.Tyr64His)

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.190T>C (p.Tyr64His)
HGVS:
  • NC_000002.12:g.189575242A>G
  • NG_009027.1:g.10570T>C
  • NM_014585.6:c.190T>CMANE SELECT
  • NP_055400.1:p.Tyr64His
  • LRG_837t1:c.190T>C
  • LRG_837:g.10570T>C
  • NC_000002.11:g.190439968A>G
  • NM_014585.5:c.190T>C
Protein change:
Y64H
Links:
dbSNP: rs1285653301
NCBI 1000 Genomes Browser:
rs1285653301
Molecular consequence:
  • NM_014585.6:c.190T>C - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001401376Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jul 16, 2021) 		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

Autosomal dominant reticuloendothelial iron overload (HFE type 4) due to a new missense mutation in the FERROPORTIN 1 gene (SLC11A3) in a large French-Canadian family.

Rivard SR, Lanzara C, Grimard D, Carella M, Simard H, Ficarella R, Simard R, D'Adamo AP, De Braekeleer M, Gasparini P.

Haematologica. 2003 Jul;88(7):824-6. No abstract available.

PubMed [citation]
PMID:
12857562

Ferroportin-related haemochromatosis associated with novel Y64H mutation of the SCL40A1 gene.

Raszeja-Wyszomirska J, Caleffi A, Milkiewicz P, Pietrangelo A.

Prz Gastroenterol. 2014;9(5):307-9. doi: 10.5114/pg.2014.46167. Epub 2014 Oct 19.

PubMed [citation]
PMID:
25396007
PMCID:
PMC4223120
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001401376.5

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

Description

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. This variant disrupts the p.Tyr64 amino acid residue in SLC40A1 (also referred to as SLC11A3). Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12857562). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed in an individual affected with ferroportin disease (PMID: 25396007). This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with histidine at codon 64 of the SLC40A1 protein (p.Tyr64His). The tyrosine residue is highly conserved and there is a moderate physicochemical difference between tyrosine and histidine.

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

Last Updated: Sep 29, 2024