NM_024426.6(WT1):c.1036A>G (p.Ser346Gly) AND Mesothelioma

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 1, 1993
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000003673.5

Allele description [Variation Report for NM_024426.6(WT1):c.1036A>G (p.Ser346Gly)]

NM_024426.6(WT1):c.1036A>G (p.Ser346Gly)

Gene:

WT1:WT1 transcription factor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p13

Genomic location:

Preferred name:

NM_024426.6(WT1):c.1036A>G (p.Ser346Gly)

Other names:

WT1, SER273GLY

HGVS:

NC_000011.10:g.32400025T>C
NG_009272.1:g.40517A>G
NM_000378.6:c.985A>G
NM_001198551.2:c.385A>G
NM_001198552.2:c.334A>G
NM_001367854.1:c.-153A>G
NM_001407044.1:c.1030A>G
NM_001407045.1:c.985A>G
NM_001407046.1:c.1036A>G
NM_001407047.1:c.913A>G
NM_001407048.1:c.985A>G
NM_001407049.1:c.985A>G
NM_001407050.1:c.862A>G
NM_001407051.1:c.274A>G
NM_024424.5:c.1036A>G
NM_024425.2:c.970A>G
NM_024426.6:c.1036A>GMANE SELECT
NP_000369.4:p.Ser329Gly
NP_001185480.1:p.Ser129Gly
NP_001185480.1:p.Ser129Gly
NP_001185481.1:p.Ser112Gly
NP_001393973.1:p.Ser344Gly
NP_001393974.1:p.Ser329Gly
NP_001393975.1:p.Ser346Gly
NP_001393976.1:p.Ser305Gly
NP_001393977.1:p.Ser329Gly
NP_001393978.1:p.Ser329Gly
NP_001393979.1:p.Ser288Gly
NP_001393980.1:p.Ser92Gly
NP_077742.3:p.Ser346Gly
NP_077743.2:p.Ser324Gly
NP_077744.3:p.Ser341Gly
NP_077744.4:p.Ser346Gly
LRG_525t1:c.1021A>G
LRG_525t2:c.385A>G
LRG_525:g.40517A>G
LRG_525p1:p.Ser341Gly
LRG_525p2:p.Ser129Gly
NC_000011.9:g.32421571T>C
NM_001198551.1:c.385A>G
NM_024426.3:c.1021A>G
NR_160306.1:n.1368A>G
NR_176266.1:n.1317A>G

Note:

NCBI staff reviewed the sequence information reported in PubMed 8401592 to determine the location of this allele on current reference sequence.

Protein change:

S112G

Links:

OMIM: 607102.0016; dbSNP: rs121907908

NCBI 1000 Genomes Browser:

rs121907908

Molecular consequence:

NM_001367854.1:c.-153A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000378.6:c.985A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001198551.2:c.385A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001198552.2:c.334A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407044.1:c.1030A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407045.1:c.985A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407046.1:c.1036A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407047.1:c.913A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407048.1:c.985A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407049.1:c.985A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407050.1:c.862A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407051.1:c.274A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_024424.5:c.1036A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_024425.2:c.970A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_024426.6:c.1036A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_160306.1:n.1368A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Mesothelioma
Synonyms:: Mesothelioma, somatic
Identifiers:: MONDO: MONDO:0005065; MedGen: C0025500

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000023836	OMIM	no assertion criteria provided	Pathogenic (Dec 1, 1993)	somatic	literature only	PubMed (2) [See all records that cite these PMIDs] 8298644, 4332312

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000023836

OMIM

no assertion criteria provided

Pathogenic
(Dec 1, 1993)

somatic

literature only

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	somatic	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Inactivation of WT1 in nephrogenic rests, genetic precursors to Wilms' tumour.

Park S, Bernard A, Bove KE, Sens DA, Hazen-Martin DJ, Garvin AJ, Haber DA.

Nat Genet. 1993 Dec;5(4):363-7.

PubMed [citation]

PMID:: 8298644

Ultrastructure and observations on the histogenesis of mesotheliomas, "adenomatoid tumors", of the female genital tract.

Salazar H, Kanbour A, Burgess F.

Cancer. 1972 Jan;29(1):141-52. No abstract available.

PubMed [citation]

PMID:: 4332312

Details of each submission

From OMIM, SCV000023836.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

Park et al. (1993) showed that the WT1 gene, in addition to being expressed in tissues of the genitourinary system, is also expressed at high levels in many supportive structures of mesodermal origin in the mouse. Furthermore, they described a case of adult human mesothelioma (156240) that contained a homozygous A-to-G transition resulting in a serine to glycine substitution at codon 273 (S273G). Normal tissue from the patient showed no evidence of this mutation, indicating that it was absent from the germline and arose as a somatic mutation within the tumor. Mesothelioma is a tumor derived from the peritoneal lining. The particular tumor studied was of the rare multicystic type which is not metastatic and has been classified as a hamartoma or a developmental abnormality of borderline malignancy (Salazar et al., 1972). Unlike most mesotheliomas, multicystic tumors are not associated with a history of asbestos exposure. Park et al. (1993) screened 32 specimens of asbestos-related mesothelioma and found no WT1 mutations. The ser273-to-gly mutation was the first reported outside the zinc finger domain that leads to an amino acid substitution rather than a termination codon. Codon 273 is highly conserved across species. Whereas wildtype WT1 represses transcription from the early growth response-1 (EGR1; 128990) promoter, following cotransfection into NIH 3T3 cells, Park et al. (1993) found that insertion of the ser273-to-gly mutation resulted in a WT1 protein that activated transcription from the EGR1 promoter.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	somatic	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 5, 2022

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