ClinVar Genomic variation as it relates to human health
NM_024426.6(WT1):c.1315C>T (p.Arg439Cys)
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_024426.6(WT1):c.1315C>T (p.Arg439Cys)
Variation ID: 3505 Accession: VCV000003505.6
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11p13 11: 32392705 (GRCh38) [ NCBI UCSC ] 11: 32414251 (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 Oct 21, 2016 Feb 4, 2024 Jun 18, 2020 - HGVS
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Nucleotide Protein Molecular
consequenceNM_024426.6:c.1315C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_077744.4:p.Arg439Cys missense NM_000378.6:c.1264C>T NP_000369.4:p.Arg422Cys missense NM_001198551.2:c.664C>T NP_001185480.1:p.Arg222Cys missense NM_001198552.2:c.613C>T NP_001185481.1:p.Arg205Cys missense NM_001367854.1:c.127C>T NP_001354783.1:p.Arg43Cys missense NM_001407044.1:c.1309C>T NP_001393973.1:p.Arg437Cys missense NM_001407045.1:c.1264C>T NP_001393974.1:p.Arg422Cys missense NM_001407046.1:c.1315C>T NP_001393975.1:p.Arg439Cys missense NM_001407047.1:c.1192C>T NP_001393976.1:p.Arg398Cys missense NM_001407049.1:c.1264C>T NP_001393978.1:p.Arg422Cys missense NM_001407050.1:c.1141C>T NP_001393979.1:p.Arg381Cys missense NM_001407051.1:c.553C>T NP_001393980.1:p.Arg185Cys missense NM_024424.5:c.1315C>T NP_077742.3:p.Arg439Cys missense NM_024425.2:c.1249C>T NP_077743.2:p.Arg417Cys missense NR_160306.1:n.1647C>T non-coding transcript variant NR_176266.1:n.1596C>T NC_000011.10:g.32392705G>A NC_000011.9:g.32414251G>A NG_009272.1:g.47837C>T LRG_525:g.47837C>T LRG_525t1:c.1300C>T LRG_525p1:p.Arg434Cys LRG_525t2:c.664C>T LRG_525p2:p.Arg222Cys - Protein change
- R222C, R422C, R205C, R439C, R43C, R381C, R398C, R185C, R437C
- Other names
- R366C
- Canonical SPDI
- NC_000011.10:32392704:G:A
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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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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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WT1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
869 | 1591 |
Conditions - Germline
Condition
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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
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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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Pathogenic (1) |
no assertion criteria provided
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Oct 1, 2007 | RCV000003680.4 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jun 18, 2020 | RCV001288153.6 |
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
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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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Pathogenic
(Mar 31, 2019)
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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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Revvity Omics, Revvity
Accession: SCV002020920.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Jun 18, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Athena Diagnostics Inc
Accession: SCV001475080.1
First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021 |
Comment:
Not found in the total gnomAD dataset, and the data is high quality. One other pathogenic or likely pathogenic variant affects the same amino acid. … (more)
Not found in the total gnomAD dataset, and the data is high quality. One other pathogenic or likely pathogenic variant affects the same amino acid. Found in multiple individuals with expected phenotype for this gene. Assessment of experimental evidence suggests this variant results in abnormal protein function. (less)
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Pathogenic
(Oct 01, 2007)
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no assertion criteria provided
Method: literature only
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MEACHAM SYNDROME
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000023843.2
First in ClinVar: Apr 04, 2013 Last updated: Oct 21, 2016 |
Comment on evidence:
In a patient with Meacham syndrome (608978), Suri et al. (2007) identified a hemizygous mutation in exon 8 of the WT1 gene, resulting in an … (more)
In a patient with Meacham syndrome (608978), Suri et al. (2007) identified a hemizygous mutation in exon 8 of the WT1 gene, resulting in an arg366-to-cys (R366C) substitution. This 46,XY infant had female external genitalia, septate uterus, double vagina, 2 ovaries, left diaphragmatic hernia, and left pulmonary hypoplasia. Death occurred at age 1 day. The unrelated parents had had 2 prior miscarriages. A mutation in this same codon (R366H; 607102.0004) has been identified in patients with Denys-Drash syndrome (194080) and diaphragmatic hernia. (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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Comprehensive genetic diagnosis of Japanese patients with severe proteinuria. | Nagano C | Scientific reports | 2020 | PMID: 31937884 |
Detailed clinical manifestations at onset and prognosis of neonatal-onset Denys-Drash syndrome and congenital nephrotic syndrome of the Finnish type. | Nishi K | Clinical and experimental nephrology | 2019 | PMID: 30963316 |
Treatment and outcome of congenital nephrotic syndrome. | Bérody S | Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association | 2019 | PMID: 29474669 |
Genotype-phenotype analysis of pediatric patients with WT1 glomerulopathy. | Ahn YH | Pediatric nephrology (Berlin, Germany) | 2017 | PMID: 27300205 |
Survey of variation in human transcription factors reveals prevalent DNA binding changes. | Barrera LA | Science (New York, N.Y.) | 2016 | PMID: 27013732 |
Clinical and molecular characterization of patients with heterozygous mutations in wilms tumor suppressor gene 1. | Lehnhardt A | Clinical journal of the American Society of Nephrology : CJASN | 2015 | PMID: 25818337 |
The Wilms' tumor suppressor Wt1 regulates Coronin 1B expression in the epicardium. | Hsu WH | Experimental cell research | 2013 | PMID: 23562652 |
Disruption of genital ridge development causes aberrant primordial germ cell proliferation but does not affect their directional migration. | Chen SR | BMC biology | 2013 | PMID: 23497137 |
The Wilms tumor gene, Wt1, maintains testicular cord integrity by regulating the expression of Col4a1 and Col4a2. | Chen SR | Biology of reproduction | 2013 | PMID: 23325811 |
WT1 mutants reveal SRPK1 to be a downstream angiogenesis target by altering VEGF splicing. | Amin EM | Cancer cell | 2011 | PMID: 22172722 |
Genetic basis of congenital and infantile nephrotic syndromes. | Lee JH | American journal of kidney diseases : the official journal of the National Kidney Foundation | 2011 | PMID: 22099579 |
WT1 mutations in Meacham syndrome suggest a coelomic mesothelial origin of the cardiac and diaphragmatic malformations. | Suri M | American journal of medical genetics. Part A | 2007 | PMID: 17853480 |
Twenty-four new cases of WT1 germline mutations and review of the literature: genotype/phenotype correlations for Wilms tumor development. | Royer-Pokora B | American journal of medical genetics. Part A | 2004 | PMID: 15150775 |
WT1 and PAX-2 podocyte expression in Denys-Drash syndrome and isolated diffuse mesangial sclerosis. | Yang Y | The American journal of pathology | 1999 | PMID: 9916932 |
Identification of constitutional WT1 mutations, in patients with isolated diffuse mesangial sclerosis, and analysis of genotype/phenotype correlations by use of a computerized mutation database. | Jeanpierre C | American journal of human genetics | 1998 | PMID: 9529364 |
Effects of Denys-Drash syndrome point mutations on the DNA binding activity of the Wilms' tumor suppressor protein WT1. | Borel F | Biochemistry | 1996 | PMID: 8810912 |
DNA binding capacity of the WT1 protein is abolished by Denys-Drash syndrome WT1 point mutations. | Little M | Human molecular genetics | 1995 | PMID: 7795587 |
Zinc finger point mutations within the WT1 gene in Wilms tumor patients. | Little MH | Proceedings of the National Academy of Sciences of the United States of America | 1992 | PMID: 1317572 |
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Text-mined citations for rs121907910 ...
HelpRecord last updated Mar 17, 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.