ClinVar Genomic variation as it relates to human health
NM_000558.5(HBA1):c.262C>T (p.His88Tyr)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000558.5(HBA1):c.262C>T (p.His88Tyr)
Variation ID: 15779 Accession: VCV000015779.4
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 16p13.3 16: 177095 (GRCh38) [ NCBI UCSC ] 16: 227094 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 May 13, 2018 Jun 9, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000558.5:c.262C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000549.1:p.His88Tyr missense NC_000016.10:g.177095C>T NC_000016.9:g.227094C>T NG_000006.1:g.37958C>T NG_046166.1:g.2578C>T NG_059186.1:g.5445C>T LRG_1225:g.5445C>T LRG_1225t1:c.262C>T LRG_1225p1:p.His88Tyr - Protein change
- H88Y
- Other names
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H87Y
- Canonical SPDI
- NC_000016.10:177094:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe 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.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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- Links
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 | ||
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| 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. |
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| HBA1 | - | - |
GRCh38 GRCh37 |
5 | 392 | |
| LOC106804613 | - | - | - | GRCh38 | 1 | 329 |
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. |
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HEMOGLOBIN M (IWATE)
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other (1) |
no assertion criteria provided
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Sep 1, 1999 | RCV000017103.7 |
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HEMOGLOBIN M (OLDENBURG)
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other (1) |
no assertion criteria provided
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Sep 1, 1999 | RCV000017105.7 |
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HEMOGLOBIN M (SENDAI)
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other (1) |
no assertion criteria provided
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Sep 1, 1999 | RCV000017106.7 |
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HEMOGLOBIN M (KANKAKEE)
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other (1) |
no assertion criteria provided
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Sep 1, 1999 | RCV000017104.7 |
| Pathogenic (1) |
criteria provided, single submitter
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- | RCV003313924.1 |
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. |
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Methemoglobinemia, alpha type
Affected status: yes
Allele origin:
unknown
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3billion
Accession: SCV004013532.1
First in ClinVar: Jul 22, 2023 Last updated: Jul 22, 2023 |
Comment:
The variant is not observed in the gnomAD v2.1.1 dataset. In silico tool predictions suggest damaging effect of the variant on gene or gene product … (more)
The variant is not observed in the gnomAD v2.1.1 dataset. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.92; 3Cnet: 0.72). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with HBA1 related disorder (PMID: 10477710). The variant has been observed in multiple (>3) similarly affected unrelated individuals (PMID: 10477710, 3957697, 6998928). Different missense changes at the same codon (p.His88Asp, p.His88Gln, p.His88Pro) have been reported to be associated with HBA1 related disorder (ClinVar ID: VCV001809522 / PMID: 18310146, 27225845). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Gestational diabetes (present) , Premature birth (present) , Small for gestational age (present) , Small for gestational age (present) , Patent ductus arteriosus (present) , … (more)
Gestational diabetes (present) , Premature birth (present) , Small for gestational age (present) , Small for gestational age (present) , Patent ductus arteriosus (present) , Cyanosis (present) , Methemoglobinemia (present) , Anemia (present) , Acrocyanosis (present) (less)
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other
(Sep 01, 1999)
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no assertion criteria provided
Method: literature only
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HEMOGLOBIN M (KANKAKEE)
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000037376.7
First in ClinVar: Apr 04, 2013 Last updated: Jun 09, 2024 |
Comment on evidence:
Hb Iwate was the first variant hemoglobin found in Japan (Shibata et al., 1960). Familial cyanosis had been recognized for about 200 years in the … (more)
Hb Iwate was the first variant hemoglobin found in Japan (Shibata et al., 1960). Familial cyanosis had been recognized for about 200 years in the prefecture of Iwate in Honshu, where about 70 affected persons were identified in the 1950s. It was called 'kuchikuro,' or 'blackmouth.' In each form of methemoglobinemia (see 617973), the heme iron is stabilized in the ferric form. Patients with the Hb M alpha forms are cyanotic at birth; those with the Hb M beta forms are usually not cyanotic until they are 3 months of age. Horst et al. (1987) showed that the Iwate mutation involves the alpha-1 globin gene. Specifically, they demonstrated a CAC-to-TAC mutation in codon 87 of that gene. They showed that the Iwate mutation can be identified directly on RsaI digestion. See Meyering et al. (1960), Shibata et al. (1961), Gerald and Efron (1961), Miyaji et al. (1962), Heller (1962), Heller et al. (1962), Tonz et al. (1962), Shibata (1964), Tamura (1964), Shimizu et al. (1965), Pik and Tonz (1966), Maggio et al. (1981), and Mayne et al. (1986). Ameri et al. (1999) likewise determined that the molecular defect in 2 patients with Hb M (Kankakee) was his87 to tyr in the HBA1 gene. The proportion of Hb M (Kankakee) observed was higher than that predicted for an alpha-1-globin variant. They presented evidence suggesting that the greater-than-expected proportion of Hb M (Kankakee) results from preferential association of the electronegative beta-globin chains with the alpha-(M)-globin chains that are more electropositive than normal alpha-globin chains. (less)
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other
(Sep 01, 1999)
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no assertion criteria provided
Method: literature only
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HEMOGLOBIN M (OLDENBURG)
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000037377.7
First in ClinVar: Apr 04, 2013 Last updated: Jun 09, 2024 |
Comment on evidence:
Hb Iwate was the first variant hemoglobin found in Japan (Shibata et al., 1960). Familial cyanosis had been recognized for about 200 years in the … (more)
Hb Iwate was the first variant hemoglobin found in Japan (Shibata et al., 1960). Familial cyanosis had been recognized for about 200 years in the prefecture of Iwate in Honshu, where about 70 affected persons were identified in the 1950s. It was called 'kuchikuro,' or 'blackmouth.' In each form of methemoglobinemia (see 617973), the heme iron is stabilized in the ferric form. Patients with the Hb M alpha forms are cyanotic at birth; those with the Hb M beta forms are usually not cyanotic until they are 3 months of age. Horst et al. (1987) showed that the Iwate mutation involves the alpha-1 globin gene. Specifically, they demonstrated a CAC-to-TAC mutation in codon 87 of that gene. They showed that the Iwate mutation can be identified directly on RsaI digestion. See Meyering et al. (1960), Shibata et al. (1961), Gerald and Efron (1961), Miyaji et al. (1962), Heller (1962), Heller et al. (1962), Tonz et al. (1962), Shibata (1964), Tamura (1964), Shimizu et al. (1965), Pik and Tonz (1966), Maggio et al. (1981), and Mayne et al. (1986). Ameri et al. (1999) likewise determined that the molecular defect in 2 patients with Hb M (Kankakee) was his87 to tyr in the HBA1 gene. The proportion of Hb M (Kankakee) observed was higher than that predicted for an alpha-1-globin variant. They presented evidence suggesting that the greater-than-expected proportion of Hb M (Kankakee) results from preferential association of the electronegative beta-globin chains with the alpha-(M)-globin chains that are more electropositive than normal alpha-globin chains. (less)
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other
(Sep 01, 1999)
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no assertion criteria provided
Method: literature only
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HEMOGLOBIN M (SENDAI)
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000037378.7
First in ClinVar: Apr 04, 2013 Last updated: Jun 09, 2024 |
Comment on evidence:
Hb Iwate was the first variant hemoglobin found in Japan (Shibata et al., 1960). Familial cyanosis had been recognized for about 200 years in the … (more)
Hb Iwate was the first variant hemoglobin found in Japan (Shibata et al., 1960). Familial cyanosis had been recognized for about 200 years in the prefecture of Iwate in Honshu, where about 70 affected persons were identified in the 1950s. It was called 'kuchikuro,' or 'blackmouth.' In each form of methemoglobinemia (see 617973), the heme iron is stabilized in the ferric form. Patients with the Hb M alpha forms are cyanotic at birth; those with the Hb M beta forms are usually not cyanotic until they are 3 months of age. Horst et al. (1987) showed that the Iwate mutation involves the alpha-1 globin gene. Specifically, they demonstrated a CAC-to-TAC mutation in codon 87 of that gene. They showed that the Iwate mutation can be identified directly on RsaI digestion. See Meyering et al. (1960), Shibata et al. (1961), Gerald and Efron (1961), Miyaji et al. (1962), Heller (1962), Heller et al. (1962), Tonz et al. (1962), Shibata (1964), Tamura (1964), Shimizu et al. (1965), Pik and Tonz (1966), Maggio et al. (1981), and Mayne et al. (1986). Ameri et al. (1999) likewise determined that the molecular defect in 2 patients with Hb M (Kankakee) was his87 to tyr in the HBA1 gene. The proportion of Hb M (Kankakee) observed was higher than that predicted for an alpha-1-globin variant. They presented evidence suggesting that the greater-than-expected proportion of Hb M (Kankakee) results from preferential association of the electronegative beta-globin chains with the alpha-(M)-globin chains that are more electropositive than normal alpha-globin chains. (less)
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|
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other
(Sep 01, 1999)
|
no assertion criteria provided
Method: literature only
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HEMOGLOBIN M (IWATE)
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000037375.7
First in ClinVar: Apr 04, 2013 Last updated: Jun 09, 2024 |
Comment on evidence:
Hb Iwate was the first variant hemoglobin found in Japan (Shibata et al., 1960). Familial cyanosis had been recognized for about 200 years in the … (more)
Hb Iwate was the first variant hemoglobin found in Japan (Shibata et al., 1960). Familial cyanosis had been recognized for about 200 years in the prefecture of Iwate in Honshu, where about 70 affected persons were identified in the 1950s. It was called 'kuchikuro,' or 'blackmouth.' In each form of methemoglobinemia (see 617973), the heme iron is stabilized in the ferric form. Patients with the Hb M alpha forms are cyanotic at birth; those with the Hb M beta forms are usually not cyanotic until they are 3 months of age. Horst et al. (1987) showed that the Iwate mutation involves the alpha-1 globin gene. Specifically, they demonstrated a CAC-to-TAC mutation in codon 87 of that gene. They showed that the Iwate mutation can be identified directly on RsaI digestion. See Meyering et al. (1960), Shibata et al. (1961), Gerald and Efron (1961), Miyaji et al. (1962), Heller (1962), Heller et al. (1962), Tonz et al. (1962), Shibata (1964), Tamura (1964), Shimizu et al. (1965), Pik and Tonz (1966), Maggio et al. (1981), and Mayne et al. (1986). Ameri et al. (1999) likewise determined that the molecular defect in 2 patients with Hb M (Kankakee) was his87 to tyr in the HBA1 gene. The proportion of Hb M (Kankakee) observed was higher than that predicted for an alpha-1-globin variant. They presented evidence suggesting that the greater-than-expected proportion of Hb M (Kankakee) results from preferential association of the electronegative beta-globin chains with the alpha-(M)-globin chains that are more electropositive than normal alpha-globin chains. (less)
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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
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Hb Grifton [α87(F8)His→Pro; HBA1: C.263A > C (or HBA2)] Causes Abnormal Pulse Oximetry Measurements. | Waters AM | Hemoglobin | 2016 | PMID: 27225845 |
| A novel hemoglobin, Bonn, causes falsely decreased oxygen saturation measurements in pulse oximetry. | Zur B | Clinical chemistry | 2008 | PMID: 18310146 |
| Identification of the molecular genetic defect of patients with methemoglobin M-Kankakee (M-Iwate), alpha87 (F8) His --> Tyr: evidence for an electrostatic model of alphaM hemoglobin assembly. | Ameri A | Blood | 1999 | PMID: 10477710 |
| Hemoglobin M Iwate is caused by a C----T transition in codon 87 of the human alpha 1-globin gene. | Horst J | Human genetics | 1987 | PMID: 3026948 |
| Hb M Iwate [alpha (2)87His----Tyr beta 2]: de novo mutation in an Irish family. | Mayne EE | Hemoglobin | 1986 | PMID: 3957697 |
| Hemoglobinopathies in Japan. | Shibata S | Hemoglobin | 1981 | PMID: 7275668 |
| Occurrence of Hb M Iwate (alpha 2 87 His leads to Tyr beta 2) in an Italian carrier. | Maggio A | Hemoglobin | 1981 | PMID: 7216821 |
| Abnormal hemoglobins in Japan. | Shibata S | Hemoglobin | 1980 | PMID: 6998928 |
| Nature of haemoglobin M-Oldenburg. | Pik C | Nature | 1966 | PMID: 5964191 |
| THE STRUCTURAL STUDY ON A NEW HEMOGLOBIN VARIANT, HB MOSAKA. | SHIMIZU A | Biochimica et biophysica acta | 1965 | PMID: 14323593 |
| [Black blood disease]. | Tamura A | Jinrui idengaku zasshi. The Japanese journal of human genetics | 1964 | PMID: 5896605 |
| Further studies on the fingerprint of Hb M-Iwate. | MIYAJI T | Nihon Ketsueki Gakkai zasshi : journal of Japan Haematological Society | 1962 | PMID: 14474785 |
| [Examination of a large hemoglobin M family. Discovery of a new hemoglobin: Hb-M-Oldenburg]. | TOENZ O | Schweizerische medizinische Wochenschrift | 1962 | PMID: 13985279 |
| Hemoglobin M Kankakee, a new variant of hemoglobin M. | HELLER P | Blood | 1962 | PMID: 13906251 |
| Spectroscopic characterization of Hb M-Iwate and Hb M-Kurume, the two variants of hemoglobin M found in Japan. | SHIBATA S | Nihon Ketsueki Gakkai zasshi : journal of Japan Haematological Society | 1961 | PMID: 13911805 |
| Chemical studies of several varieties of Hb M. | GERALD PS | Proceedings of the National Academy of Sciences of the United States of America | 1961 | PMID: 13897827 |
| Studies on the heterogeneity of hemoglobin. I. The heterogeneity of different human hemoglobin types in carboxymethylcellulose and in amberlite IRC-50 chromatography qualitative aspects. | HUISMAN TH | Clinica chimica acta; international journal of clinical chemistry | 1960 | PMID: 13852555 |
| Heller, P. Hemoglobin M (Chicago) and M (Kankakee). In: Lehmann, H., Betke, K. (eds.) Haemoglobin-Colloquium. Stuttgart: Georg Thieme Verlag (pub.) 47-49, 1962. | - | - | - | - |
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Text-mined citations for rs28928876 ...
HelpRecord last updated Jun 10, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.