NM_000518.4(HBB):c.364G>A (p.Glu122Lys) AND Hb SS disease

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: May 9, 2018
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000202511.16

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:: Hb SS disease (SCD)
Synonyms:: Sickle cell anemia; Sickle cell disease; HbS disease; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011382; MedGen: C0002895; Orphanet: 232; OMIM: 603903

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000190692	GeneReviews	no classification provided	not provided	germline	literature only
SCV001163644	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001423601	Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 9, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000190692

GeneReviews

no classification provided

not provided

germline

literature only

SCV001163644

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001423601

Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(May 9, 2018)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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, literature only
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneReviews, SCV000190692.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	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

From Baylor Genetics, SCV001163644.1

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

#	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

From Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital, SCV001423601.1

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

Description

[ACMG/AMP: PS4, PM2, PM3, PP5] This alteration has a prevalence that is significantly increased compared with controls (RR/OR > 5; CI does not include 1.0) [PS4], is absent from or rarely observed in large-scale population databases [PM2], is detected in trans with a known pathogenic variant [PM3], was reported as a pathogenic/likely pathogenic alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory) [PP5].

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

Last Updated: Jul 5, 2025

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