ClinVar Genomic variation as it relates to human health
NM_000545.8(HNF1A):c.293C>T (p.Ala98Val)
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_000545.8(HNF1A):c.293C>T (p.Ala98Val)
Variation ID: 129233 Accession: VCV000129233.28
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 12q24.31 12: 120979061 (GRCh38) [ NCBI UCSC ] 12: 121416864 (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 17, 2014 May 1, 2024 Feb 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000545.8:c.293C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000536.6:p.Ala98Val missense NM_001306179.2:c.293C>T NP_001293108.2:p.Ala98Val missense NC_000012.12:g.120979061C>T NC_000012.11:g.121416864C>T NG_011731.2:g.5316C>T LRG_522:g.5316C>T LRG_522t1:c.293C>T - Protein change
- A98V
- Other names
- p.A98V:GCC>GTC
- Canonical SPDI
- NC_000012.12:120979060: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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0.01997 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.01807
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.01858
1000 Genomes Project 0.01997
1000 Genomes Project 30x 0.02030
The Genome Aggregation Database (gnomAD) 0.02065
The Genome Aggregation Database (gnomAD), exomes 0.02900
Exome Aggregation Consortium (ExAC) 0.03672
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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HNF1A | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
875 | 961 |
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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Benign (7) |
criteria provided, multiple submitters, no conflicts
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Apr 26, 2017 | RCV000117230.18 | |
Benign (1) |
criteria provided, single submitter
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Mar 6, 2018 | RCV000391875.6 | |
Benign (1) |
criteria provided, single submitter
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Feb 1, 2019 | RCV000445439.5 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
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Feb 1, 2024 | RCV000713791.10 | |
Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Sep 18, 2018 | RCV002226424.4 | |
Benign (1) |
criteria provided, single submitter
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Jan 1, 2022 | RCV003153378.2 | |
Benign (1) |
criteria provided, single submitter
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Jul 7, 2023 | RCV003315672.1 |
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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Benign
(-)
|
criteria provided, single submitter
Method: clinical testing
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NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000305105.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
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Benign
(Aug 31, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Athena Diagnostics
Accession: SCV000844423.1
First in ClinVar: Oct 20, 2018 Last updated: Oct 20, 2018 |
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Benign
(Apr 26, 2017)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000707747.2
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
Number of individuals with the variant: 1
Sex: mixed
|
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Likely benign
(Sep 18, 2018)
|
criteria provided, single submitter
Method: clinical testing
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Maturity onset diabetes mellitus in young
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002747827.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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Benign
(Mar 04, 2013)
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criteria provided, single submitter
Method: clinical testing
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AllHighlyPenetrant
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV000151403.1
First in ClinVar: May 17, 2014 Last updated: May 17, 2014 |
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Benign
(May 19, 2014)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000168822.10
First in ClinVar: Jun 23, 2014 Last updated: Oct 02, 2016 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
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Benign
(Mar 06, 2018)
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criteria provided, single submitter
Method: clinical testing
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Maturity-onset diabetes of the young type 3
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000376710.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
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Benign
(-)
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criteria provided, single submitter
Method: research
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Maturity onset diabetes mellitus in young
(Autosomal dominant inheritance)
Affected status: no
Allele origin:
somatic
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Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic
Accession: SCV002505383.1
First in ClinVar: Apr 30, 2022 Last updated: Apr 30, 2022 |
Comment:
Mutations in this gene can predispose to MODY3. It is associated with both micro and macrovascular complications of diabetes, especially cardiovascular complications. Associated with glucosuria. … (more)
Mutations in this gene can predispose to MODY3. It is associated with both micro and macrovascular complications of diabetes, especially cardiovascular complications. Associated with glucosuria. Good response to sulfonylureas. However, rs1800574 localized in the DNA-binding domain of the HNF1A gene (p.Ala98Val) doesn't directly predispose to early-onset Diabetes Mellitus even if the prevalence of the variant is high. (less)
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001726692.4
First in ClinVar: Jun 15, 2021 Last updated: Feb 14, 2024 |
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Benign
(Feb 01, 2019)
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criteria provided, single submitter
Method: research
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Monogenic diabetes
Affected status: unknown
Allele origin:
unknown
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Personalized Diabetes Medicine Program, University of Maryland School of Medicine
Accession: SCV000537086.3
First in ClinVar: Mar 14, 2017 Last updated: Jun 13, 2020 |
Comment:
ACMG criteria: BA1 (overall MAF in gnomAD 3%, 6.6% in South Asian in gnomAD, ~3% in other subpop), BS2 (346 cases and 404 controls in … (more)
ACMG criteria: BA1 (overall MAF in gnomAD 3%, 6.6% in South Asian in gnomAD, ~3% in other subpop), BS2 (346 cases and 404 controls in T2DM ) [Revel score 0.597, PP3 (6), BP4 (4)= conflicting evidence, not using] [not using BP6]: benign (less)
Number of individuals with the variant: 26
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Benign
(Jan 01, 2022)
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criteria provided, single submitter
Method: clinical testing
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Ovarian cancer
Affected status: yes
Allele origin:
germline
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Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University
Accession: SCV003843348.1
First in ClinVar: Mar 26, 2023 Last updated: Mar 26, 2023 |
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Benign
(Jul 07, 2023)
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criteria provided, single submitter
Method: clinical testing
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Nonpapillary renal cell carcinoma
Affected status: yes
Allele origin:
germline
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KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV004015761.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001798964.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001929653.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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not provided
(Sep 19, 2013)
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no classification provided
Method: reference population
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AllHighlyPenetrant
Affected status: unknown
Allele origin:
germline
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ITMI
Accession: SCV000085359.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014
Comment:
Please see associated publication for description of ethnicities
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Observation 1:
Ethnicity/Population group: Whole_cohort
Observation 2:
Ethnicity/Population group: African
Observation 3:
Ethnicity/Population group: African_European
Observation 4:
Ethnicity/Population group: Central_Asian
Observation 5:
Ethnicity/Population group: East_Asian
Observation 6:
Ethnicity/Population group: European
Observation 7:
Ethnicity/Population group: Hispanic
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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
HelpTitle | Author | Journal | Year | Link |
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HNF1A Mutations and Beta Cell Dysfunction in Diabetes. | Miyachi Y | International journal of molecular sciences | 2022 | PMID: 35328643 |
HNF1A gene p.I27L is associated with early-onset, maturity-onset diabetes of the young-like diabetes in Turkey. | Beysel S | BMC endocrine disorders | 2019 | PMID: 31109344 |
The Common HNF1A Variant I27L Is a Modifier of Age at Diabetes Diagnosis in Individuals With HNF1A-MODY. | Locke JM | Diabetes | 2018 | PMID: 29895593 |
Occurrence of amino acid mutation (Ala98Val) of HNF1α in association with type II diabetes. | Shakya P | Journal of Nepal Health Research Council | 2014 | PMID: 25575005 |
Prevalence of HNF1A (MODY3) mutations in a Norwegian population (the HUNT2 Study). | Eide SA | Diabetic medicine : a journal of the British Diabetic Association | 2008 | PMID: 18513305 |
Common variants in maturity-onset diabetes of the young genes and future risk of type 2 diabetes. | Holmkvist J | Diabetes | 2008 | PMID: 18332101 |
Four novel mutations, including the first gross deletion in TCF1, identified in HNF-4alpha, GCK and TCF1 in patients with MODY in Israel. | Stern E | Journal of pediatric endocrinology & metabolism : JPEM | 2007 | PMID: 17937063 |
Structural basis of disease-causing mutations in hepatocyte nuclear factor 1beta. | Lu P | Biochemistry | 2007 | PMID: 17924661 |
The impact of genotype frequencies on the clinical validity of genomic profiling for predicting common chronic diseases. | Janssens AC | Genetics in medicine : official journal of the American College of Medical Genetics | 2007 | PMID: 17700391 |
Variants of the transcription factor 7-like 2 (TCF7L2) gene are associated with type 2 diabetes in an African-American population enriched for nephropathy. | Sale MM | Diabetes | 2007 | PMID: 17601994 |
Mutations in GCK and HNF-1alpha explain the majority of cases with clinical diagnosis of MODY in Spain. | Estalella I | Clinical endocrinology | 2007 | PMID: 17573900 |
Genetic predisposition to type 2 diabetes among Asian Indians. | Radha V | The Indian journal of medical research | 2007 | PMID: 17496355 |
Etiology of early-onset type 2 diabetes in Indians: islet autoimmunity and mutations in hepatocyte nuclear factor 1alpha and mitochondrial gene. | Sahu RP | The Journal of clinical endocrinology and metabolism | 2007 | PMID: 17440016 |
Insights on pathogenesis of type 2 diabetes from MODY genetics. | Weedon MN | Current diabetes reports | 2007 | PMID: 17425917 |
Screening of 134 single nucleotide polymorphisms (SNPs) previously associated with type 2 diabetes replicates association with 12 SNPs in nine genes. | Willer CJ | Diabetes | 2007 | PMID: 17192490 |
GCK and HNF1alpha mutations and polymorphisms in Polish women with gestational diabetes. | Zurawek M | Diabetes research and clinical practice | 2007 | PMID: 16963153 |
HNF-1alpha G574S is a functional variant with decreased transactivation activity. | Navalón-García K | Diabetic medicine : a journal of the British Diabetic Association | 2006 | PMID: 17116178 |
Common variants in HNF-1 alpha and risk of type 2 diabetes. | Holmkvist J | Diabetologia | 2006 | PMID: 17033837 |
Mutations in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha (HNF1A) and 4 alpha (HNF4A) in maturity-onset diabetes of the young. | Ellard S | Human mutation | 2006 | PMID: 16917892 |
A prevalent amino acid polymorphism at codon 98 (Ala98Val) of the hepatocyte nuclear factor-1alpha is associated with maturity-onset diabetes of the young and younger age at onset of type 2 diabetes in Asian Indians. | Anuradha S | Diabetes care | 2005 | PMID: 16186275 |
A large-scale association analysis of common variation of the HNF1alpha gene with type 2 diabetes in the U.K. Caucasian population. | Weedon MN | Diabetes | 2005 | PMID: 16046319 |
Half of clinically defined maturity-onset diabetes of the young patients in Denmark do not have mutations in HNF4A, GCK, and TCF1. | Johansen A | The Journal of clinical endocrinology and metabolism | 2005 | PMID: 15928245 |
A genome search for genetic determinants that influence plasma fibrinogen levels. | Soria JM | Arteriosclerosis, thrombosis, and vascular biology | 2005 | PMID: 15761192 |
Polymorphic variations in the neurogenic differentiation-1, neurogenin-3, and hepatocyte nuclear factor-1alpha genes contribute to glucose intolerance in a South Indian population. | Jackson AE | Diabetes | 2004 | PMID: 15277395 |
Transcription factor 1 and beta-cell function in glucose-tolerant subjects. | Chiu KC | Diabetic medicine : a journal of the British Diabetic Association | 2003 | PMID: 12675668 |
Newly defined genetic diabetes syndromes: maturity onset diabetes of the young. | Winter WE | Reviews in endocrine & metabolic disorders | 2003 | PMID: 12618559 |
Hepatocyte nuclear factor-1 alpha gene mutations and diabetes in Norway. | Bjørkhaug L | The Journal of clinical endocrinology and metabolism | 2003 | PMID: 12574234 |
The role of transcription factors in maturity-onset diabetes of the young. | Mitchell SM | Molecular genetics and metabolism | 2002 | PMID: 12359128 |
Role of common sequence variants in insulin secretion in familial type 2 diabetic kindreds: the sulfonylurea receptor, glucokinase, and hepatocyte nuclear factor 1alpha genes. | Elbein SC | Diabetes care | 2001 | PMID: 11289470 |
Identification and functional analysis of mutations in the hepatocyte nuclear factor-1alpha gene in anti-islet autoantibody-negative Japanese patients with type 1 diabetes. | Kawasaki E | The Journal of clinical endocrinology and metabolism | 2000 | PMID: 10634407 |
Three new mutations in the hepatocyte nuclear factor-1alpha gene in Japanese subjects with diabetes mellitus: clinical features and functional characterization. | Yoshiuchi I | Diabetologia | 1999 | PMID: 10333057 |
Mutations in the hepatocyte nuclear factor-1alpha/MODY3 gene in Japanese subjects with early- and late-onset NIDDM. | Iwasaki N | Diabetes | 1997 | PMID: 9287053 |
A prevalent amino acid polymorphism at codon 98 in the hepatocyte nuclear factor-1alpha gene is associated with reduced serum C-peptide and insulin responses to an oral glucose challenge. | Urhammer SA | Diabetes | 1997 | PMID: 9133564 |
Genetic variation in the hepatocyte nuclear factor-1 alpha gene in Danish Caucasians with late-onset NIDDM. | Urhammer SA | Diabetologia | 1997 | PMID: 9112026 |
Mutations in the hepatocyte nuclear factor-1alpha gene in maturity-onset diabetes of the young (MODY3). | Yamagata K | Nature | 1996 | PMID: 8945470 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=HNF1A | - | - | - | - |
type2diabetesgenetics.org | - | - | - | - |
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Text-mined citations for rs1800574 ...
HelpRecord last updated May 08, 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.