NM_000518.5(HBB):c.199A>G (p.Lys67Glu) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 18, 2022
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:: RCV000985737.3

Allele description [Variation Report for NM_000518.5(HBB):c.199A>G (p.Lys67Glu)]

NM_000518.5(HBB):c.199A>G (p.Lys67Glu)

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.199A>G (p.Lys67Glu)

Other names:

K66E; Hb I-Toulouse

HGVS:

NC_000011.10:g.5226693T>C
NG_000007.3:g.70923A>G
NG_042296.1:g.224T>C
NG_046672.1:g.4628T>C
NG_059281.1:g.5379A>G
NM_000518.5:c.199A>GMANE SELECT
NP_000509.1:p.Lys67Glu
LRG_1232t1:c.199A>G
LRG_1232:g.5379A>G
LRG_1232p1:p.Lys67Glu
NC_000011.9:g.5247923T>C
NM_000518.4:c.199A>G

Protein change:

K67E; LYS66GLU

Links:

HBVAR: 366; OMIM: 141900.0116; dbSNP: rs34165323

NCBI 1000 Genomes Browser:

rs34165323

Molecular consequence:

NM_000518.5:c.199A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001134213	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Likely pathogenic (Sep 18, 2022)	unknown	clinical testing	PubMed (7) [See all records that cite these PMIDs] 7928379, 7407240, 19429541, 5791730, 3583764, 35898763, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001134213

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Likely pathogenic
(Sep 18, 2022)

unknown

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Hb I-Toulouse [beta 66(E10)Lys->Glu] in association with alpha-thalassemia.

Hendy JG, Cauchi MN.

Hemoglobin. 1994 May;18(3):227-9. No abstract available.

PubMed [citation]

PMID:: 7928379

Oxidation properties of two hemoglobin variants with their mutation localized in the heme pocket: Hb Castilla beta 32 (B14) Leu replaced by Arg and Hb Toulouse beta 66 (E10) Lys replaced by Glu, and abnormal functional properties of Hb Castilla.

Thillet J, Garel MC, Bierme R, Rosa J.

Biochim Biophys Acta. 1980 Jul 24;624(1):293-303. No abstract available.

PubMed [citation]

PMID:: 7407240

See all PubMed Citations (7)

Details of each submission

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV001134213.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

It has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, individuals heterozygous for this variant present with chronic mild hemolytic anemia (PMID: 35898763 (2022), 7928379 (1994), 3583764 (1987), 5791730 (1969)). In a functional study, this variant exhibited minor alterations in function in an assay that evaluated oxidation and reduction rates (PMID: 7407240 (1980)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, this variant is classified as likely pathogenic.

#	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

Last Updated: Jan 6, 2024

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