NM_000518.4(HBB):c.364G>A (p.Glu122Lys) AND beta Thalassemia

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 17, 2019
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:: RCV000029993.14

Allele description [Variation Report for NM_000518.4(HBB):c.364G>A (p.Glu122Lys)]

NM_000518.4(HBB):c.364G>A (p.Glu122Lys)

Genes:

LOC110006319:beta-globin gene 3' regulatory region [Gene]
HBB:hemoglobin subunit beta [Gene - OMIM - HGNC]
LOC107133510:origin of replication at HBB [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.4

Genomic location:

Preferred name:

NM_000518.4(HBB):c.364G>A (p.Glu122Lys)

Other names:

E121K

HGVS:

NC_000011.10:g.5225678C>T
NG_000007.3:g.71938G>A
NG_046672.1:g.3613C>T
NG_053049.1:g.1999C>T
NG_059281.1:g.6394G>A
NM_000518.5:c.364G>AMANE SELECT
NP_000509.1:p.Glu122Lys
NP_000509.1:p.Glu122Lys
LRG_1232t1:c.364G>A
LRG_1232:g.6394G>A
LRG_1232p1:p.Glu122Lys
NC_000011.9:g.5246908C>T
NM_000518.4:c.364G>A
P68871:p.Glu122Lys

Protein change:

E122K; Glu121Lys

Links:

HBVAR: 510; UniProtKB: P68871#VAR_003049; OMIM: 141900.0202; OMIM: 141900.0245; OMIM: 141900.0507; dbSNP: rs33946267

NCBI 1000 Genomes Browser:

rs33946267

Molecular consequence:

NM_000518.5:c.364G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: beta Thalassemia (BTHAL)
Synonyms:: Cooley's anemia; Erythroblastic anemia; Mediterranean anemia
Identifiers:: MONDO: MONDO:0019402; MedGen: C0005283; Orphanet: 848

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001194054	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Women's Health Autosomal Recessive and X-Linked Classification Criteria (2019))	Pathogenic (Dec 17, 2019)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 1112610, 893136, 5481775 Citation Link,
SCV002089186	Natera, Inc.	no assertion criteria provided	Pathogenic (Mar 17, 2017)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001194054

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Women's Health Autosomal Recessive and X-Linked Classification Criteria (2019))

Pathogenic
(Dec 17, 2019)

unknown

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link,

SCV002089186

Natera, Inc.

no assertion criteria provided

Pathogenic
(Mar 17, 2017)

germline

clinical testing

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Twelve families with Hb O Arab in the Burgas district of Bulgaria. Observations on sixteen examples of Hb O Arab-beta (0) thalassaemia.

Kantchev KN, Tcholakov BN, Casey R, Lehmann H, El Hazmi M.

Humangenetik. 1975;26(2):93-7. No abstract available.

PubMed [citation]

PMID:: 1112610

Homozygous hemoglobin O Arab in a gypsy family in Yugoslavia.

Efremov GD, Sadikario A, Stojancov A, Dojcinov D, Huisman TH.

Hemoglobin. 1977;1(4):389-94. No abstract available.

PubMed [citation]

PMID:: 893136

See all PubMed Citations (3)

Details of each submission

From Myriad Genetics, Inc., SCV001194054.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

NM_000518.4(HBB):c.364G>A(E122K, aka Hb O-Arab) is classified as pathogenic in the context of Hb beta chain-related hemoglobinopathy and is associated with hemoglobin O-Arab. Sources cited for classification include the following: PMID 1112610, 893136 and 5481775. Classification of NM_000518.4(HBB):c.364G>A(E122K, aka Hb O-Arab) is based on the following criteria: This is a well-established pathogenic variant in the literature that has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Natera, Inc., SCV002089186.1

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

#	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: Jul 13, 2025

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