VCV000268131.4 - ClinVar

NM_000121.4(EPOR):c.1316G>A (p.Trp439Ter)

Germline

Classification

criteria provided, single submitter. Learn more about how ClinVar calculates review status.

Likely pathogenic
Likely pathogenic (1)

1 out of 2 submissions contributed to this 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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000121.4(EPOR):c.1316G>A (p.Trp439Ter)

Variation ID: 268131 Accession: VCV000268131.4

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 19p13.2 19: 11378195 (GRCh38) [ NCBI UCSC ] 19: 11488871 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Nov 22, 2016	Oct 1, 2022	Sep 1, 2020

HGVS

Nucleotide	Protein	Molecular consequence
NM_000121.4:c.1316G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000112.1:p.Trp439Ter	nonsense
NR_033663.2:n.1673G>A		non-coding transcript variant
NC_000019.10:g.11378195C>T
NC_000019.9:g.11488871C>T
NG_021395.1:g.11148G>A

... more HGVS ... less HGVS

Protein change

W439*

Other names

Canonical SPDI

NC_000019.10:11378194:C:T

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA10602669 dbSNP: rs121917830 VarSome

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.
EPOR		-	-	GRCh38 GRCh37	173	195

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.
Primary familial polycythemia due to EPO receptor mutation	not provided (1)	no classification provided	-	RCV000258849.10
Acute megakaryoblastic leukemia without down syndrome	Likely pathogenic (1)	criteria provided, single submitter	Sep 1, 2020	RCV001293750.9

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.	Expand all rows Collapse all rows 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.
Likely pathogenic (Sep 01, 2020) C Contributing to aggregate classification	criteria provided, single submitter (AMP Guidelines, 2017)	Acute megakaryoblastic leukemia without down syndrome	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia Accession: SCV001480503.1 First in ClinVar: Mar 07, 2021 Last updated: Mar 07, 2021	Observation: 1 Collection method: clinical testing Allele origin: somatic Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: somatic Affected status: yes Number of individuals with the variant: 1 Platform type: Next-gen sequencing panel

not provided (-) N Not contributing to aggregate classification	no classification provided	Primary familial polycythemia due to EPO receptor mutation	GeneReviews Accession: SCV000328592.2 First in ClinVar: Nov 22, 2016 Last updated: Oct 01, 2022	Publications: PubMed (2) PubMed: 17488692‚ 8506290 BookShelf: NBK395975 BookShelf: NBK395975 Observation: 1 Collection method: literature only Allele origin: germline Affected status: yes Observation 1 Collection method: literature only Allele origin: germline Affected status: yes

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Primary Familial and Congenital Erythrocytosis.	Adam MP	-	2025	PMID: 27831681
Molecular genetic analyses in familial and sporadic congenital primary erythrocytosis.	Rives S	Haematologica	2007	PMID: 17488692
Truncated erythropoietin receptor causes dominantly inherited benign human erythrocytosis.	de la Chapelle A	Proceedings of the National Academy of Sciences of the United States of America	1993	PMID: 8506290

Text-mined citations for rs121917830 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Aug 08, 2026