NM_213653.4(HJV):c.238T>C (p.Cys80Arg) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 11, 2023
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:: RCV001851583.5

Allele description [Variation Report for NM_213653.4(HJV):c.238T>C (p.Cys80Arg)]

NM_213653.4(HJV):c.238T>C (p.Cys80Arg)

Gene:

HJV:hemojuvelin BMP co-receptor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q21.1

Genomic location:

Preferred name:

NM_213653.4(HJV):c.238T>C (p.Cys80Arg)

HGVS:

NC_000001.11:g.146019594A>G
NG_011568.1:g.7229T>C
NM_001316767.2:c.-22+104T>C
NM_001379352.1:c.238T>C
NM_145277.5:c.-102T>C
NM_202004.4:c.-22+104T>C
NM_213652.4:c.-21-894T>C
NM_213653.4:c.238T>CMANE SELECT
NP_001366281.1:p.Cys80Arg
NP_998818.1:p.Cys80Arg
NC_000001.10:g.145415419T>C
Q6ZVN8:p.Cys80Arg

Protein change:

C80R; CYS80ARG

Links:

UniProtKB: Q6ZVN8#VAR_019617; OMIM: 608374.0005; dbSNP: rs28940586

NCBI 1000 Genomes Browser:

rs28940586

Molecular consequence:

NM_145277.5:c.-102T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001316767.2:c.-22+104T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_202004.4:c.-22+104T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_213652.4:c.-21-894T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001379352.1:c.238T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_213653.4:c.238T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002155778	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 11, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 14982867, 15710580, 18827264, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002155778

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 11, 2023)

germline

clinical testing

PubMed (4)
[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

Genetic abnormalities and juvenile hemochromatosis: mutations of the HJV gene encoding hemojuvelin.

Lee PL, Beutler E, Rao SV, Barton JC.

Blood. 2004 Jun 15;103(12):4669-71. Epub 2004 Feb 24.

PubMed [citation]

PMID:: 14982867

Hemojuvelin (HJV)-associated hemochromatosis: analysis of HJV and HFE mutations and iron overload in three families.

Wallace DF, Dixon JL, Ramm GA, Anderson GJ, Powell LW, Subramaniam N.

Haematologica. 2005 Feb;90(2):254-5.

PubMed [citation]

PMID:: 15710580

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV002155778.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 80 of the HJV protein (p.Cys80Arg). This variant is present in population databases (rs28940586, gnomAD 0.004%). This missense change has been observed in individual(s) with clinical features of juvenile hemochromatosis (PMID: 14982867, 15710580). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 2369). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects HJV function (PMID: 18827264). This variant disrupts the p.Cys80 amino acid residue in HJV. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as 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: Feb 20, 2024

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