VCV000446743.3 - ClinVar

NM_000518.4(HBB):c.[295G>A;98T>A]

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.

(1)

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.

other

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

This haplotype includes the following variants

NM_000518.4(HBB):c.[295G>A;98T>A]

Other names: HBB, VAL98MET AND LEU32GLN
Hb Medicine Lake
Functional consequence: -
Links: ClinGen: CA037825; OMIM: 141900.0452

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 MEDICINE LAKE	other (1)	no assertion criteria provided	Dec 12, 2017	RCV000016807.12

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 MEDICINE LAKE Affected status: not provided Allele origin: germline	OMIM Accession: SCV000037077.4 First in ClinVar: Apr 04, 2013 Last updated: Jul 24, 2016	Publications: PubMed (1) PubMed: 7860732 Coleman, M. B., Adams, J. G., (more...) Coleman, M. B., Adams, J. G., Smith, C. M., Steinberg, M. H. Modulation of Hb Koln disease by an additional mutation: Hb Medicine Lake. (Abstract) Blood 82 (suppl. 1): 222a, 1993. Comment on evidence: Coleman et al. (1993, 1995) investigated the molecular basis of transfusion-dependent hemolytic anemia in a Caucasian female infant who rapidly developed the phenotype of beta-thalassemia … (more) Coleman et al. (1993, 1995) investigated the molecular basis of transfusion-dependent hemolytic anemia in a Caucasian female infant who rapidly developed the phenotype of beta-thalassemia major. Both the father and mother were normal hematologically. The DNA sequence of one HBB allele demonstrated 2 mutations, one for the moderately unstable Hb Koln (141900.0151) and another for a novel leu32-to-gln change resulting from a CTG to CAG transversion. The new hemoglobin was called Hb Medicine Lake. The hydrophilic gln32 has an uncharged polar side chain that may distort the B helix and provoke further molecular instability. Biosynthesis studies of this mutation showed a deficit of beta-globin synthesis with early loss of beta-globin chains. Coleman et al. (1995) pointed to 14 previously described hemoglobin variants with 2 mutations in the same polypeptide chain. Most of these rare disorders had probably arisen via homologous crossing over. Such a mechanism, however, could not account for the Hb Medicine Lake, since neither parent had a detectable abnormal hemoglobin gene. Therefore, it was presumed that this was a true double de novo mutation. (less)

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
Report on Ten Years' Experience of Premarital Hemoglobinopathy Screening at a Center in Antalya, Southern Turkey.	Canatan D	Hemoglobin	2016	PMID: 27207683
Molecular characteristics of three hemoglobin variants observed in a Chinese population: Hb Ube-1 [β98 (FG5) Val→Met], Hb Ube‑2 [α68 (E17) Asn→Asp] and Hb Ube‑4 [α116 (GH4) Glu→Ala].	Huang Y	Molecular medicine reports	2011	PMID: 21523319
Comprehensive and efficient HBB mutation analysis for detection of beta-hemoglobinopathies in a pan-ethnic population.	Chan OT	American journal of clinical pathology	2010	PMID: 20395516
Abnormal hemoglobin phenotypes in carriers of mild anemia in Latin America.	Zamaro PJ	Genetics and molecular research : GMR	2010	PMID: 20309827
Initiation codon mutation (ATG --> ATA) of the beta-globin gene causing beta-thalassemia in a Swedish family.	Landin B	American journal of hematology	1995	PMID: 7864023
Two missense mutations in the beta-globin gene can cause severe beta thalassemia. Hemoglobin Medicine Lake (beta 32[B14]leucine-->glutamine; 98 [FG5] valine-->methionine).	Coleman MB	The Journal of clinical investigation	1995	PMID: 7860732
Two missense mutations in the beta-globin gene can cause severe beta thalassemia. Hemoglobin Medicine Lake (beta 32[B14]leucine-->glutamine; 98 [FG5] valine-->methionine).	Coleman MB	The Journal of clinical investigation	1995	PMID: 7860732
Hemoglobin Köln occurring in association with a beta zero thalassemia: hematologic and functional consequences.	Galacteros F	Blood	1989	PMID: 2752127
Hemoglobin Köln: direct analysis of the gene mutation by synthetic DNA probes.	Horst J	Blood	1986	PMID: 3768534
beta 0 thalassemia, a nonsense mutation in man.	Chang JC	Proceedings of the National Academy of Sciences of the United States of America	1979	PMID: 88735
Oxygen transport in hemoglobin Köln. Effect of increased oxygen affinity in absence of compensatory erythrocytosis.	Woodson RD	Archives of internal medicine	1974	PMID: 4414970
Identical substitution in Hb Ube-1 and Hb Köln.	Ohba Y	Nature: New biology	1973	PMID: 4514958
Unstable haemoglobin Köln disease in members of a Malay family.	Eng LL	Journal of medical genetics	1972	PMID: 5079107
Oxygen affinity in hemoglobin Köln disease.	De Furia FG	Blood	1972	PMID: 5059650
Hemoglobin Köln disease occurring as a fresh mutation: erythrocyte metabolism and survival.	Miller DR	Blood	1971	PMID: 4942314
Köln haemoglobinopathy. Further data and a comparison with other hereditary Heinz body anaemias.	Jones RV	British journal of haematology	1967	PMID: 6067323
Haemoglobin sydney: Beta-67 (E11) valine modified to alanine: an emerging pattern of unstable haemoglobins.	Carrell RW	Nature	1967	PMID: 6050213
A West Australian family with a haemolytic disorder associated with haemoglobin Köln.	Jackson JM	British journal of haematology	1967	PMID: 6029950
[Hemoglobin Köln disease: familial hypochromic hemolytic anemia with hemoglobin anomaly].	Pribilla W	Klinische Wochenschrift	1965	PMID: 5881530
Hemoglobin M disease in Japan.	Shibata S	Israel journal of medical sciences	1965	PMID: 5856115
HEREDITARY HEINZ-BODY ANAEMIA, THROMBOCYTOPENIA, AND HAEMOGLOBINOPATHY (HB KOELN) IN A GLASGOW FAMILY.	HUTCHISON HE	British medical journal	1964	PMID: 14198723
Bradley, T. B., Wohl, R. C., Murphy, S. B., Oski, F. A., Bunn, H. F. Properties of hemoglobin Bryn Mawr, beta85 phe-to-ser, a new spontaneous mutation producing an unstable hemoglobin with high oxygen affinity. (Abstract) Blood 40: 947, 1972.	-	-	-	-
Coleman, M. B., Adams, J. G., Smith, C. M., Steinberg, M. H. Modulation of Hb Koln disease by an additional mutation: Hb Medicine Lake. (Abstract) Blood 82 (suppl. 1): 222a, 1993.	-	-	-	-
Pribilla, W. Thalassemie-aehnliche Erkrankung mit neuem minor-Hb (Hb Koln). In: Lehmann, H., Betke, K. Haemoglobin-Colloquium. Stuttgart: Georg Thieme Verlag (pub.) 1-14, 1962.	-	-	-	-
click to load more click to collapse

Text-mined citations for this variant ...

Record last updated Nov 25, 2024

ClinVar Genomic variation as it relates to human health

NM_000518.4(HBB):c.[295G>A;98T>A]

Variant Details

NM_000518.4(HBB):c.[295G>A;98T>A]

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...