ClinVar Genomic variation as it relates to human health
NM_000458.4(HNF1B):c.1325T>C (p.Met442Thr)
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_000458.4(HNF1B):c.1325T>C (p.Met442Thr)
Variation ID: 36839 Accession: VCV000036839.5
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q12 17: 37704931 (GRCh38) [ NCBI UCSC ] 17: 36064938 (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 Apr 4, 2013 Dec 11, 2022 Jul 6, 2019 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000458.4:c.1325T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000449.1:p.Met442Thr missense NM_001165923.4:c.1247T>C NP_001159395.1:p.Met416Thr missense NM_001304286.2:c.1247T>C NP_001291215.1:p.Met416Thr missense NC_000017.11:g.37704931A>G NC_000017.10:g.36064938A>G NG_013019.2:g.45176T>C - Protein change
- M442T, M416T
- Other names
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- Canonical SPDI
- NC_000017.11:37704930:A:G
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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
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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
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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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HNF1B | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh38 GRCh37 |
600 | 812 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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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Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jul 6, 2019 | RCV000030520.4 | |
Likely risk allele (1) |
criteria provided, single submitter
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- | RCV002464083.1 |
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
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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
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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
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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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Likely risk allele
(-)
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criteria provided, single submitter
(K & H Uppaluri Personalized Medicine Clinic Variant Classification & Assertion Criteria_Updated V.1)
Method: research
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Maturity onset diabetes mellitus in young
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
unknown
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Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic
Accession: SCV002605435.1
First in ClinVar: Dec 11, 2022 Last updated: Dec 11, 2022 |
Comment:
HNF1B gene mutations are associated with early onset diabetes and pancreatic atrophy. It is also associated with multiple renal manifestations including renal cysts, Tubulointerstitial disease, … (more)
HNF1B gene mutations are associated with early onset diabetes and pancreatic atrophy. It is also associated with multiple renal manifestations including renal cysts, Tubulointerstitial disease, glomerulocystic disease, renal hypoplasia, hypomagnesemia.However no sufficient evidence is found to ascertain the role of this particular variant rs193922482, yet. (less)
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Likely pathogenic
(Jul 06, 2019)
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criteria provided, single submitter
Method: literature only
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Renal cysts and diabetes syndrome
Affected status: yes
Allele origin:
germline
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Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg
Accession: SCV000926001.1
First in ClinVar: Jul 14, 2019 Last updated: Jul 14, 2019
Comment:
This variant and it's classification has been reported by Vasileiou et al. 2019; DOI:10.1101/576918. The variants has previously been reported in ClinVar:36839; PMID:29207974 as "NM_000458.3(HNF1B):c.1325T>C … (more)
This variant and it's classification has been reported by Vasileiou et al. 2019; DOI:10.1101/576918. The variants has previously been reported in ClinVar:36839; PMID:29207974 as "NM_000458.3(HNF1B):c.1325T>C (p.Met442Thr)" with clinical significance Likely pathogenic. It has been re-classified using InterVar and manual curation as Likely pathogenic based on PM1 PM2 PP3 PP5. (less)
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likely pathogenic
(Aug 18, 2011)
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criteria provided, single submitter
Method: curation, clinical testing
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MODY5
(autosomal unknown)
Affected status: yes, unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000053191.2
First in ClinVar: Apr 04, 2013 Last updated: Mar 28, 2022 |
Comment:
Converted during submission to Likely pathogenic.
Observation 1:
Tissue: Blood
Observation 2:
Tissue: Blood
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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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A novel splice-site mutation of the HNF1B gene in a family with maturity onset diabetes of the young type 5 (MODY5). | Fujita Y | Endocrinology, diabetes & metabolism case reports | 2020 | PMID: 33434175 |
Spectrum of mutations in monogenic diabetes genes identified from high-throughput DNA sequencing of 6888 individuals. | Bansal V | BMC medicine | 2017 | PMID: 29207974 |
Elucidating the Mutational Landscape in Hepatocyte Nuclear Factor 1β (HNF1B) by Computational Approach. | Sneha P | Advances in protein chemistry and structural biology | 2017 | PMID: 28215227 |
The role of hepatocyte nuclear factor 1β in disease and development. | El-Khairi R | Diabetes, obesity & metabolism | 2016 | PMID: 27615128 |
Hypomagnesemia as First Clinical Manifestation of ADTKD-HNF1B: A Case Series and Literature Review. | van der Made CI | American journal of nephrology | 2015 | PMID: 26340261 |
Hepatic phenotypes of HNF1B gene mutations: a case of neonatal cholestasis requiring portoenterostomy and literature review. | Kotalova R | World journal of gastroenterology | 2015 | PMID: 25741167 |
HNF1B-associated renal and extra-renal disease-an expanding clinical spectrum. | Clissold RL | Nature reviews. Nephrology | 2015 | PMID: 25536396 |
The HNF1B score is a simple tool to select patients for HNF1B gene analysis. | Faguer S | Kidney international | 2014 | PMID: 24897035 |
HNF1B-related diabetes triggered by renal transplantation. | Zuber J | Nature reviews. Nephrology | 2009 | PMID: 19639018 |
- | - | - | - | DOI: 10.1101/576918 |
Text-mined citations for this variant ...
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.