ClinVar Genomic variation as it relates to human health
NM_000209.4(PDX1):c.714GCC[6] (p.Pro244_Gly245insPro)
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.
Uncertain significance(1); Benign(9)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000209.4(PDX1):c.714GCC[6] (p.Pro244_Gly245insPro)
Variation ID: 36412 Accession: VCV000036412.24
- Type and length
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Microsatellite, 3 bp
- Location
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Cytogenetic: 13q12.2 13: 27924562-27924563 (GRCh38) [ NCBI UCSC ] 13: 28498712-28498714 (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 May 1, 2024 Jan 29, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000209.4:c.714GCC[6] MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000200.1:p.Pro244_Gly245insPro inframe insertion NM_000209.4:c.726_728dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
inframe insertion NM_000209.4:c.726_728dupGCC MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
inframe insertion NM_000209.3:c.726_728dup NC_000013.11:g.27924563GCC[6] NC_000013.10:g.28498700GCC[6] NG_008183.1:g.9533GCC[6] - Protein change
- Other names
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- Canonical SPDI
- NC_000013.11:27924562:GCCGCCGCCGCCGCC:GCCGCCGCCGCCGCCGCC
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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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0.01877 (GCCGCCGCCGCCGCCGCC)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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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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PDX1 | - | - |
GRCh38 GRCh37 |
162 | 198 |
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 (2) |
criteria provided, multiple submitters, no conflicts
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May 28, 2019 | RCV000030082.11 | |
Uncertain significance (1) |
criteria provided, single submitter
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Aug 18, 2011 | RCV000030084.10 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
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Oct 10, 2019 | RCV000261035.16 | |
Benign (3) |
criteria provided, multiple submitters, no conflicts
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Jan 29, 2024 | RCV000959390.17 | |
Benign (1) |
criteria provided, single submitter
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Dec 7, 2018 | RCV000445549.11 | |
risk factor (1) |
no assertion criteria provided
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Nov 1, 1999 | RCV002279932.9 | |
Benign (1) |
criteria provided, single submitter
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Sep 18, 2017 | RCV002381270.9 |
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
(Jan 10, 2019)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001916107.2
First in ClinVar: Sep 24, 2021 Last updated: Jun 10, 2023 |
Comment:
This variant is associated with the following publications: (PMID: 16229747, 17003361, 14764823, 10545531, 27634015)
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uncertain
(Aug 18, 2011)
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criteria provided, single submitter
Method: curation, clinical testing
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Neonatal Diabetes Mellitus
(autosomal recessive)
Affected status: yes, unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000052739.2
First in ClinVar: Apr 04, 2013 Last updated: Apr 11, 2022 |
Comment:
Converted during submission to Uncertain significance.
Observation 1:
Number of individuals with the variant: 5
Observation 2:
Number of individuals with the variant: 5
Observation 3:
Tissue: Blood
Observation 4:
Tissue: Blood
Observation 5:
Tissue: Blood
Observation 6:
Tissue: Blood
Observation 7:
Tissue: Blood
Observation 8:
Tissue: Blood
Observation 9:
Tissue: Blood
Observation 10:
Tissue: Blood
Observation 11:
Tissue: Blood
Observation 12:
Tissue: Blood
Observation 13:
Tissue: Blood
Observation 14:
Tissue: Blood
Observation 15:
Tissue: Blood
Observation 16:
Tissue: Blood
Observation 17:
Tissue: Blood
Observation 18:
Tissue: Blood
Observation 19:
Tissue: Blood
Observation 20:
Tissue: Blood
Observation 21:
Tissue: Blood
Observation 22:
Tissue: Blood
Observation 23:
Tissue: Blood
Observation 24:
Tissue: Blood
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benign
(Aug 18, 2011)
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criteria provided, single submitter
Method: clinical testing
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MODY4
(autosomal unknown)
Affected status: not provided
Allele origin:
not applicable
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000052737.2
First in ClinVar: Apr 04, 2013 Last updated: Apr 11, 2022 |
Comment:
Converted during submission to Benign.
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Benign
(Oct 10, 2019)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
unknown
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Athena Diagnostics
Accession: SCV001476621.1
First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021 |
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Benign
(Sep 18, 2017)
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criteria provided, single submitter
Method: clinical testing
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Maturity onset diabetes mellitus in young
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002672498.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as 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
(Jun 25, 2015)
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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: SCV000332347.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
Number of individuals with the variant: 1
Sex: mixed
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Benign
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Maturity-onset diabetes of the young type 4
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001138926.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Benign
(Jan 29, 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: SCV001106293.5
First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024 |
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Benign
(Nov 06, 2023)
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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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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV004563019.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
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Benign
(Dec 07, 2018)
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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: SCV000537093.2
First in ClinVar: Mar 14, 2017 Last updated: Jun 13, 2020 |
Comment:
ACMG criteria: BP4 (CADD and indel predictor PROVEAN calls neutral, DDIG-indel 90% probability that it is neurtal), BA1 (7.5% in African and 38 homo in … (more)
ACMG criteria: BP4 (CADD and indel predictor PROVEAN calls neutral, DDIG-indel 90% probability that it is neurtal), BA1 (7.5% in African and 38 homo in gnomAD), PM4 (nonframeshift protein length changing), PS3 (decrease in insulin promoter activity, PMID: 10545531), PP1mod (2 familes with 5 individuals each segregating, PMID: 10545531- 1999 paper, only looked at PDX1 variant)--> conflicting data BUT 7.5% in African --> BA1= benign (less)
Number of individuals with the variant: 17
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risk factor
(Nov 01, 1999)
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no assertion criteria provided
Method: literature only
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TYPE 2 DIABETES MELLITUS, SUSCEPTIBILITY TO
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000029629.4
First in ClinVar: Apr 04, 2013 Last updated: Jan 26, 2024 |
Comment on evidence:
Hani et al. (1999) investigated 192 French, non-MODY type 2 diabetic families (125853) and identified 3 novel IPF1 mutations, including 2 substitutions (Q59L, 600733.0003 and … (more)
Hani et al. (1999) investigated 192 French, non-MODY type 2 diabetic families (125853) and identified 3 novel IPF1 mutations, including 2 substitutions (Q59L, 600733.0003 and D76N, 600733.0002) and an in-frame proline insertion, insCCG243. Functional transactivation assays of these IPF1 mutant isoforms in a beta-pancreatic tumor cell line transfected with a transcriptional reporter and IPF1 expression plasmids demonstrated a significant inhibition of basal insulin promoter activity (stronger with the insCCG243 mutant). They found that the insCCG243 mutation was linked, in 2 families, to an autosomal dominant-like late-onset form of type 2 diabetes, in which insulin secretion became progressively impaired. The lower-penetrance D76N and Q59L mutations were more prevalent and were associated with a relative risk of 12.6 for diabetes and with decreased glucose-stimulated insulin secretion in nondiabetic subjects. They proposed that IPF1 mutations can cause MODY or apparently monogenic late-onset diabetes and that they represent a significant risk factor for type 2 diabetes. (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
HelpTitle | Author | Journal | Year | Link |
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Role of a proline insertion in the insulin promoter factor 1 (IPF1) gene in African Americans with type 2 diabetes. | Elbein SC | Diabetes | 2006 | PMID: 17003361 |
Insulin Promoter Factor 1 variation is associated with type 2 diabetes in African Americans. | Karim MA | BMC medical genetics | 2005 | PMID: 16229747 |
Pancreas duodenum homeobox-1 transcriptional activation requires interactions with p300. | Stanojevic V | Endocrinology | 2004 | PMID: 15001545 |
Insulin promoter factor-1 mutations and diabetes in Trinidad: identification of a novel diabetes-associated mutation (E224K) in an Indo-Trinidadian family. | Cockburn BN | The Journal of clinical endocrinology and metabolism | 2004 | PMID: 14764823 |
Newly defined genetic diabetes syndromes: maturity onset diabetes of the young. | Winter WE | Reviews in endocrine & metabolic disorders | 2003 | PMID: 12618559 |
Pancreas duodenum homeobox-1 regulates pancreas development during embryogenesis and islet cell function in adulthood. | Hui H | European journal of endocrinology | 2002 | PMID: 11834421 |
Mutations in the insulin promoter factor-1 gene in late-onset type 2 diabetes mellitus. | Reis AF | European journal of endocrinology | 2000 | PMID: 11022198 |
Defective mutations in the insulin promoter factor-1 (IPF-1) gene in late-onset type 2 diabetes mellitus. | Hani EH | The Journal of clinical investigation | 1999 | PMID: 10545531 |
Text-mined citations for rs193922357 ...
HelpRecord last updated Aug 18, 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.