NM_000518.5(HBB):c.327C>R (p.Asn109Lys) AND HEMOGLOBIN PRESBYTERIAN

Clinical significance:other (Last evaluated: Dec 12, 2017)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000016558.7

Allele description [Variation Report for NM_000518.5(HBB):c.327C>R (p.Asn109Lys)]

NM_000518.5(HBB):c.327C>R (p.Asn109Lys)

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_000518.5(HBB):c.327C>R (p.Asn109Lys)
Other names:
N108K
HGVS:
  • NC_000011.10:g.5225715G>Y
  • NG_046672.1:g.3650G>Y
  • NG_053049.1:g.2036G>Y
  • NG_059281.1:g.6357C>R
  • NM_000518.5:c.327C>RMANE SELECT
  • NP_000509.1:p.Asn109Lys
  • NP_000509.1:p.Asn109Lys
  • LRG_1232t1:c.327C>R
  • LRG_1232:g.6357C>R
  • LRG_1232p1:p.Asn109Lys
  • NC_000011.9:g.5246945G>Y
  • NM_000518.4:c.327C>R
Protein change:
N109K; ASN108LYS
Links:
OMIM: 141900.0226; dbSNP: rs34933751
NCBI 1000 Genomes Browser:
rs34933751
Molecular consequence:
  • NM_000518.5:c.327C>R - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
HEMOGLOBIN PRESBYTERIAN
Identifiers:

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000036826OMIMno assertion criteria providedother
(Dec 12, 2017)
germlineliterature only

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Hemoglobin Ohio (beta 142 Ala replaced by): a new abnormal hemoglobin with high oxygen affinity and erythrocytosis.

Moo-Penn WF, Schneider RG, Shih T, Jones RT, Govindarajan S, Govindarajan PG, Patchen LC.

Blood. 1980 Aug;56(2):246-50.

PubMed [citation]
PMID:
7397380

DNA restriction mapping identifies the chromosome carrying the mutant Hb Presbyterian beta-globin gene.

Horst J, Oehme R, Kleihauer E, Kohne E.

Hum Genet. 1983;64(3):263-6.

PubMed [citation]
PMID:
6309649
See all PubMed Citations (5)

Details of each submission

From OMIM, SCV000036826.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (5)

Description

See Moo-Penn et al. (1978), Horst et al. (1983), and Villegas et al. (1986). Using PCR and direct sequencing, Schnee et al. (1990) demonstrated that the molecular defect is a C-to-G substitution in codon 108; this eliminates an MaeII restriction site.

The beta variant lys108 enhances the stability of hemoglobin in the deoxy-state, conferring low affinity for oxygen binding in vitro. Suzuki et al. (2002) generated mutant mice carrying the Presbyterian mutation at the beta-globin locus by a targeted knockin strategy. Heterozygous mice showed the expression of Hb Presbyterian in 27.7% of total peripheral blood without any hematologic abnormalities, which well mimicked human cases. On the other hand, homozygous mice exclusively expressed Hb Presbyterian in 100% of peripheral blood associated with hemolytic anemia, Heinz body formation, and splenomegaly. Hb Presbyterian showed instability in an in vitro precipitation assay. Erythrocytes from homozygous mice showed a shortened life span when transfused into wildtype mice, confirming that the knocked-in mutation of lys108 caused hemolysis in homozygous mice. Suzuki et al. (2002) stated that this was the first report on the hemolytic anemia of unstable hemoglobin in an animal model. The results confirmed the notion that the higher ratio of an unstable variant beta-globin chain in erythrocytes triggers the pathologic precipitation and induces hemolysis in abnormal hemoglobinopathies.

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

Last Updated: Oct 16, 2021

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