VCV000000561.1 - ClinVar

NM_000140.3(FECH):c.[1224T>A;1225C>T;1231T>G]

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

This haplotype includes the following variants

NM_000140.3(FECH):c.[1224T>A;1225C>T;1231T>G]

Other names: FECH, ASN408LYS, PRO409SER, AND CYS411GLY
Functional consequence: -
Links: ClinGen: CA026511; OMIM: 612386.0014

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
FECH		-	-	GRCh38 GRCh37	315	412

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Protoporphyria, erythropoietic, 1	Pathogenic (1)	no assertion criteria provided	Aug 15, 2000	RCV000000591.5

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Aug 15, 2000)	no assertion criteria provided Method: literature only	PROTOPORPHYRIA, ERYTHROPOIETIC, 1 Affected status: not provided Allele origin: germline	OMIM Accession: SCV000020740.3 First in ClinVar: Apr 04, 2013 Last updated: Jun 22, 2018	Publications: PubMed (1) PubMed: 10942404 Comment on evidence: In a patient with erythropoietic protoporphyria (EPP1; 177000), Schneider-Yin et al. (2000) found heterozygosity for a triple mutation in the FECH gene: 1224T-A, 1225C-T, and … (more) In a patient with erythropoietic protoporphyria (EPP1; 177000), Schneider-Yin et al. (2000) found heterozygosity for a triple mutation in the FECH gene: 1224T-A, 1225C-T, and 1231T-G, leading to asn408-to-lys/pro409-to-ser/cys411-to-gly amino acid changes. All 3 mutations were absent from the FECH gene of the patient's mother, suggesting that all 3 were aligned on the FECH allele derived from the father. (less)

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Clinical and molecular epidemiology of erythropoietic protoporphyria in Italy.	Ventura P	European journal of dermatology : EJD	2020	PMID: 33021473
Strong correlation of ferrochelatase enzymatic activity with Mitoferrin-1 mRNA in lymphoblasts of patients with protoporphyria.	Phillips J	Molecular genetics and metabolism	2019	PMID: 30391163
Diagnostic Delay in Erythropoietic Protoporphyria.	Lala SM	The Journal of pediatrics	2018	PMID: 30041937
Clinical, Biochemical, and Genetic Characterization of North American Patients With Erythropoietic Protoporphyria and X-linked Protoporphyria.	Balwani M	JAMA dermatology	2017	PMID: 28614581
Identification of FECH gene multiple variations in two Chinese patients with erythropoietic protoporphyria and a review.	Long ZB	Journal of Zhejiang University. Science. B	2016	PMID: 27704751
Loss-of-function ferrochelatase and gain-of-function erythroid-specific 5-aminolevulinate synthase mutations causing erythropoietic protoporphyria and x-linked protoporphyria in North American patients reveal novel mutations and a high prevalence of X-linked protoporphyria.	Balwani M	Molecular medicine (Cambridge, Mass.)	2013	PMID: 23364466
Molecular epidemiology of erythropoietic protoporphyria in the U.K.	Whatley SD	The British journal of dermatology	2010	PMID: 20105171
Contribution of a common single-nucleotide polymorphism to the genetic predisposition for erythropoietic protoporphyria.	Gouya L	American journal of human genetics	2006	PMID: 16385445
Genotypic determinants of phenotype in North American patients with erythropoietic protoporphyria.	Risheg H	Molecular genetics and metabolism	2003	PMID: 14567969
Mutations in the iron-sulfur cluster ligands of the human ferrochelatase lead to erythropoietic protoporphyria.	Schneider-Yin X	Blood	2000	PMID: 10942404
Mutations in the iron-sulfur cluster ligands of the human ferrochelatase lead to erythropoietic protoporphyria.	Schneider-Yin X	Blood	2000	PMID: 10942404
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Text-mined citations for this variant ...

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_000140.3(FECH):c.[1224T>A;1225C>T;1231T>G]

Variant Details

NM_000140.3(FECH):c.[1224T>A;1225C>T;1231T>G]

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...