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NM_000518.5(HBB):c.190C>T (p.His64Tyr) AND beta Thalassemia

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Jul 2, 2019
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000988480.2

Allele description [Variation Report for NM_000518.5(HBB):c.190C>T (p.His64Tyr)]

NM_000518.5(HBB):c.190C>T (p.His64Tyr)

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.190C>T (p.His64Tyr)
Other names:
H63Y; Hb M-Saskatoon; Hb Hörlein-Weber; Hb Leipzig; Hb M-Arhus; Hb M-Chicago; Hb M-Emory; Hb M-Erlangen; Hb M-Hamburg; Hb M-Hida; Hb M-Kurume; Hb M-Radom; Hb Novi Sad
HGVS:
  • NC_000011.10:g.5226702G>A
  • NG_000007.3:g.70914C>T
  • NG_042296.1:g.233G>A
  • NG_046672.1:g.4637G>A
  • NG_059281.1:g.5370C>T
  • NM_000518.5:c.190C>TMANE SELECT
  • NP_000509.1:p.His64Tyr
  • LRG_1232t1:c.190C>T
  • LRG_1232:g.5370C>T
  • LRG_1232p1:p.His64Tyr
  • NC_000011.9:g.5247932G>A
  • NM_000518.4:c.190C>T
  • P68871:p.His64Tyr
Protein change:
H64Y; HIS63TYR
Links:
HBVAR: 359; UniProtKB: P68871#VAR_002957; OMIM: 141900.0165; dbSNP: rs33922873
NCBI 1000 Genomes Browser:
rs33922873
Molecular consequence:
  • NM_000518.5:c.190C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
beta Thalassemia (BTHAL)
Synonyms:
Cooley's anemia; Erythroblastic anemia; Mediterranean anemia
Identifiers:
MONDO: MONDO:0019402; MedGen: C0005283; Orphanet: 848

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001138217Mendelics
criteria provided, single submitter

(Mendelics Assertion Criteria 2017)		Pathogenic
(May 28, 2019) 		unknownclinical testing

Citation Link,

SCV001360657Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Jul 2, 2019) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Haemoglobin M Saskatoon and haemoglobin M Hyde Park in two Yugoslavian families.

Efremov GD, Huisman TH, Stanulovic M, Zurovec M, Duma H, Wilson JB, Jeremic V.

Scand J Haematol. 1974;13(1):48-60. No abstract available.

PubMed [citation]
PMID:
4413625

HEREDITARY CYANOSIS.

Baltzan DM, Sugarman H.

Can Med Assoc J. 1950 Apr;62(4):348-50. No abstract available.

PubMed [citation]
PMID:
20324533
PMCID:
PMC1591883
See all PubMed Citations (6)

Details of each submission

From Mendelics, SCV001138217.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001360657.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

Variant summary: HBB c.190C>T (p.His64Tyr) results in a conservative amino acid change located in a heme binding site (InterPro) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251426 control chromosomes (gnomAD). The variant (also known as Hb M-Saskatoon) is widely regarded as causing hemoglobin M (HbM) disease, and has been reported in the literature in several affected individuals (e.g. Efremov_1974, Waye_1994, Suryantoro_1995, Kedar_2005, Brunner-Agten_2010, Garcia-Morin_2019). The disorder was observed to be inherited in an autosomal dominant pattern, often occurring as a de novo mutation. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Jan 7, 2023