NM_000518.5(HBB):c.205C>T (p.Leu69Phe) AND none provided

Clinical significance:Pathogenic (Last evaluated: Dec 12, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001286462.2

Allele description [Variation Report for NM_000518.5(HBB):c.205C>T (p.Leu69Phe)]

NM_000518.5(HBB):c.205C>T (p.Leu69Phe)

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.205C>T (p.Leu69Phe)
Other names:
L68F
HGVS:
  • NC_000011.10:g.5226687G>A
  • NG_000007.3:g.70929C>T
  • NG_042296.1:g.218G>A
  • NG_046672.1:g.4622G>A
  • NG_053049.1:g.3008G>A
  • NG_059281.1:g.5385C>T
  • NM_000518.5:c.205C>TMANE SELECT
  • NP_000509.1:p.Leu69Phe
  • LRG_1232t1:c.205C>T
  • LRG_1232:g.5385C>T
  • LRG_1232p1:p.Leu69Phe
  • NC_000011.9:g.5247917G>A
  • NM_000518.4:c.205C>T
Protein change:
L69F; LEU68PHE
Links:
OMIM: 141900.0523; OMIM: 141900.0524; dbSNP: rs33961459
NCBI 1000 Genomes Browser:
rs33961459
Molecular consequence:
  • NM_000518.5:c.205C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
none provided
Identifiers:
MedGen: CN235283

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001473037ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratoriescriteria provided, single submitter
Pathogenic
(Dec 12, 2019)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001473037.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The Hb Loves Park variant (HBB: c.205C>T; p.Leu69Phe, also known as Leu68Phe when numbered from the mature protein, rs33961459) is reported in the literature in the heterozygous state in multiple individuals affected with microcytic anemia (Ferreira 2006, HbVar database and references therein). In one instance, this variant was observed in an affected proband but was not found in either parent despite demonstrated parentage, indicating a de novo origin (Ferreira 2006). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The leucine at codon 69 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Additionally, another amino acid substitution at this codon (p.Leu69Pro, also known as Hb Mizuho) has been reported de novo in multiple individuals with hemolytic anemia and is considered disease-causing (HbVar database and references therein). Based on available information, the Hb Loves Park variant is considered to be pathogenic. References: Link to Hb Loves Park in HbVar: http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=375 Link to Hb Mizuho in HbVar: http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=373 Ferreira C et al. Hemoglobin Loves Park [beta68 (E12) Leu-->Phe]: report of five cases including one originating from a de novo mutation. Am J Hematol. 2006 Apr;81(4):256-61.

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

Last Updated: Nov 27, 2021

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