VCV000015117.2 - ClinVar

NM_000518.4(HBB):c.206T>A (p.Leu69His)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(3)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic; other

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000518.4(HBB):c.206T>A (p.Leu69His)

Variation ID: 15117 Accession: VCV000015117.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 11p15.4 11: 5226686 (GRCh38) [ NCBI UCSC ] 11: 5247916 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Mar 25, 2018	May 28, 2018	Dec 12, 2017

HGVS

Nucleotide	Protein	Molecular consequence
NM_000518.5:c.206T>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000509.1:p.Leu69His	missense
NC_000011.10:g.5226686A>T
NC_000011.9:g.5247916A>T
NG_000007.3:g.70930T>A
NG_042296.1:g.217A>T
NG_046672.1:g.4621A>T
NG_053049.1:g.3007A>T
NG_059281.1:g.5386T>A
LRG_1232:g.5386T>A
LRG_1232t1:c.206T>A	LRG_1232p1:p.Leu69His
	P68871:p.Leu69His

... more HGVS ... less HGVS

Protein change

L69H

Other names

L68H

Canonical SPDI

NC_000011.10:5226685:A:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

HBVAR: 374 ClinGen: CA124762 UniProtKB: P68871#VAR_002964 OMIM: 141900.0029 dbSNP: rs33972593 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
HBB		-	-	GRCh38 GRCh37	22	1835
LOC106099062	-	-	-	GRCh38	-	863
LOC107133510	-	-	-	GRCh38	-	1785

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
HEMOGLOBIN BRISBANE	other (1)	no assertion criteria provided	Dec 12, 2017	RCV000016272.5
HEMOGLOBIN GREAT LAKES	other (1)	no assertion criteria provided	Dec 12, 2017	RCV000016273.5
Erythrocytosis, familial, 6	Pathogenic (1)	no assertion criteria provided	Jan 1, 1983	RCV000641416.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
other (Dec 12, 2017)	no assertion criteria provided Method: literature only	HEMOGLOBIN BRISBANE Affected status: not provided Allele origin: germline	OMIM Accession: SCV000036540.5 First in ClinVar: Apr 04, 2013 Last updated: Mar 25, 2018	Publications: PubMed (2) PubMed: 6166590‚ 6629830 Rahbar, S., Lee, T., Asmeron, Y. Hb (more...) Rahbar, S., Lee, T., Asmeron, Y. Hb Beckman alpha135 (H13) ala-to-glu: a new unstable variant and reduced oxygen affinity. (Abstract) Blood 78 (suppl. 1): 204a, 1991. Comment on evidence: See Brennan et al. (1981), Rahbar et al. (1981), and Williamson et al. (1983).
other (Dec 12, 2017)	no assertion criteria provided Method: literature only	HEMOGLOBIN GREAT LAKES Affected status: not provided Allele origin: germline	OMIM Accession: SCV000036541.5 First in ClinVar: Apr 04, 2013 Last updated: Mar 25, 2018	Publications: PubMed (2) PubMed: 6166590‚ 6629830 Rahbar, S., Lee, T., Asmeron, Y. Hb (more...) Rahbar, S., Lee, T., Asmeron, Y. Hb Beckman alpha135 (H13) ala-to-glu: a new unstable variant and reduced oxygen affinity. (Abstract) Blood 78 (suppl. 1): 204a, 1991. Comment on evidence: See Brennan et al. (1981), Rahbar et al. (1981), and Williamson et al. (1983).
Pathogenic (Jan 01, 1983)	no assertion criteria provided Method: literature only	ERYTHROCYTOSIS 6 Affected status: not provided Allele origin: germline	OMIM Accession: SCV000763057.1 First in ClinVar: May 28, 2018 Last updated: May 28, 2018	Publications: PubMed (2) PubMed: 6166590‚ 6629830 Rahbar, S., Lee, T., Asmeron, Y. Hb (more...) Rahbar, S., Lee, T., Asmeron, Y. Hb Beckman alpha135 (H13) ala-to-glu: a new unstable variant and reduced oxygen affinity. (Abstract) Blood 78 (suppl. 1): 204a, 1991. Comment on evidence: See Brennan et al. (1981), Rahbar et al. (1981), and Williamson et al. (1983).

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Hb Brisbane (beta 68 (E12) Leu replaced by His) is unstable.	Williamson D	Hemoglobin	1983	PMID: 6629830
Hemoglobin Brisbane: beta68 Leu replaced by His. A new high oxygen affinity variant.	Brennan SO	Hemoglobin	1981	PMID: 6166590
Rahbar, S., Lee, T., Asmeron, Y. Hb Beckman alpha135 (H13) ala-to-glu: a new unstable variant and reduced oxygen affinity. (Abstract) Blood 78 (suppl. 1): 204a, 1991.	-	-	-	-

Text-mined citations for rs33972593 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Apr 25, 2022

ClinVar Genomic variation as it relates to human health

NM_000518.4(HBB):c.206T>A (p.Leu69His)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs33972593 ...