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NM_000518.5(HBB):c.20A>T (p.Glu7Val) AND Sickle cell-hemoglobin C disease

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Feb 17, 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:
RCV003150808.8

Allele description [Variation Report for NM_000518.5(HBB):c.20A>T (p.Glu7Val)]

NM_000518.5(HBB):c.20A>T (p.Glu7Val)

Genes:
LOC106099062:HBB recombination 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_000518.5(HBB):c.20A>T (p.Glu7Val)
Other names:
E6V; HbS
HGVS:
  • NC_000011.10:g.5227002T>A
  • NG_000007.3:g.70614A>T
  • NG_042296.1:g.533T>A
  • NG_046672.1:g.4937T>A
  • NG_059281.1:g.5070A>T
  • NM_000518.5:c.20A>TMANE SELECT
  • NP_000509.1:p.Glu7Val
  • NP_000509.1:p.Glu7Val
  • LRG_1232t1:c.20A>T
  • LRG_1232:g.5070A>T
  • LRG_1232p1:p.Glu7Val
  • NC_000011.9:g.5248232T>A
  • NM_000518.4:c.20A>T
  • P68871:p.Glu7Val
Protein change:
E7V; Glu6Val
Links:
Genetic Testing Registry (GTR): GTR000500319; UniProtKB: P68871#VAR_002863; OMIM: 141900.0039; OMIM: 141900.0040; OMIM: 141900.0243; OMIM: 141900.0244; OMIM: 141900.0245; OMIM: 141900.0246; OMIM: 141900.0247; OMIM: 141900.0521; OMIM: 141900.0523; dbSNP: rs334
NCBI 1000 Genomes Browser:
rs334
Molecular consequence:
  • NM_000518.5:c.20A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Sickle cell-hemoglobin C disease
Synonyms:
Hemoglobin SC disease; Sickle cell-hemoglobin C disease syndrome; Hemoglobin S/C
Identifiers:
MONDO: MONDO:0016669; MeSH: D006450; MedGen: C0019034; Orphanet: 251365

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003839051Johns Hopkins Genomics, Johns Hopkins University
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Feb 17, 2023) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Hearing impairment in persons with the hemoglobin SC genotype.

Onakoya PA, Nwaorgu OG, Shokunbi WA.

Ear Nose Throat J. 2010 Jul;89(7):306-10.

PubMed [citation]
PMID:
20628988

Effect of amino acid at the beta 6 position on surface hydrophobicity, stability, solubility, and the kinetics of polymerization of hemoglobin. Comparisons among Hb A (Glu beta 6), Hb C (Lys beta 6), Hb Machida (Gln beta 6), and Hb S (Val beta 6).

Adachi K, Kim J, Travitz R, Harano T, Asakura T.

J Biol Chem. 1987 Sep 25;262(27):12920-5.

PubMed [citation]
PMID:
2888754
See all PubMed Citations (5)

Details of each submission

From Johns Hopkins Genomics, Johns Hopkins University, SCV003839051.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This HBB variant (rs334) reaches polymorphic frequency (>1%) within the African/African American subpopulation in a large population dataset (gnomAD: 1121/24964 total alleles; 4.49%; 4 homozygotes) and has been reported in ClinVar. It is the most common pathogenic HBB variant in individuals of African ancestry. Also known as p.Glu6Val and HbS, it has been reported in a homozygous or compound heterozygous state in individuals with beta-hemoglobinopathies. One bioinformatic tool queried predicts that this substitution would damaging, while another predicts it would be tolerated. Experimental studies have shown that this variant affects the physical and kinetic properties of the hemoglobin protein. Bioinformatic analysis predicts that this missense variant would not affect normal exon 1 splicing, although this has not been confirmed experimentally to our knowledge. We consider c.20A>T (p.Glu7Val) to be pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 10, 2024