UniProtKB/Swiss-Prot P19544: Variant p.Arg394Trp

Wilms tumor protein
Gene: WT1
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Variant information Variant position:

394 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Arginine (R) to Tryptophan (W) at position 394 (R394W, p.Arg394Trp). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties:

Change from large size and basic (R) to large size and aromatic (W) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-3 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:

Lowest score: -4 (low probability of substitution).
Highest score: 11 (high probability of substitution).

More information can be found on the following page
Variant description:

In DDS, WT1, MEACHS and NPHS4. Any additional useful information about the variant.

Sequence information Variant position:

394 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

449 The length of the canonical sequence.
Location on the sequence:

QRRHTGVKPFQCKTCQRKFS R SDHLKTHTRTHTGKTSEKPF The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         QRRHTGVKPFQCKTCQRKFSRSDHLKTHTRTHTGKTSEKPF

Mouse                         QRRHTGVKPFQCKTCQRKFSRSDHLKTHTRTHTGKTSEKPF

Rat                           QRRHTGVKPFQCKTCQRKFSRSDHLKTHTRTHTGKTSEKPF

Pig                           QRRHTGVKPFQCKTCQRKFSRSDHLKTHTRTHTGKTSEKPF

Xenopus tropicalis            QRRHTGIKPFQCKTCQRKFSRSDHLKTHTRTHTG---EKPF

Sequence annotation in neighborhood:

The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:

Type: the type of sequence feature.
Positions: endpoints of the sequence feature.
Description: contains additional information about the feature.

Type	Positions	Description
Chain	1 – 449	Wilms tumor protein
Zinc finger	383 – 405	C2H2-type 3
Region	393 – 401	Important for interaction with target DNA
Mutagenesis	394 – 394	R -> AS. Strongly reduced binding of DNA and RNA.

Literature citations
Germline intronic and exonic mutations in the Wilms' tumour gene (WT1) affecting urogenital development.
Bruening W.; Bardeesy N.; Silverman B.L.; Cohn R.A.; Machin G.A.; Aronson A.J.; Housman D.; Pelletier J.;
Nat. Genet. 1:144-148(1992)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 385-405; VARIANTS DDS TYR-330; PRO-394 AND TRP-394; Molecular analysis of two Japanese cases of Denys-Drash syndrome.
Tsuda M.; Sakiyama T.; Kitagawa T.; Watanabe S.; Watanabe T.; Takahashi S.; Kawaguchi H.; Ito K.;
J. Inherit. Metab. Dis. 16:876-880(1993)
Cited for: VARIANTS DDS TRP-394 AND PRO-398; Mutational screening of the Wilms's tumour gene, WT1, in males with genital abnormalities.
Clarkson P.A.; Davies H.R.; Williams D.M.; Chaudhary R.; Hughes I.A.; Patterson M.N.;
J. Med. Genet. 30:767-772(1993)
Cited for: VARIANTS DDS TYR-360 AND TRP-394; 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.; Denamur E.; Henry I.; Cabanis M.-O.; Luce S.; Cecille A.; Elion J.; Peuchmaur M.; Loirat C.; Niaudet P.; Gubler M.-C.; Junien C.;
Am. J. Hum. Genet. 62:824-833(1998)
Cited for: VARIANTS NPHS4 TYR-377; LEU-383 AND ASN-396; VARIANTS DDS CYS-366; GLN-394; TRP-394 AND PRO-398; VARIANT WT1 ASN-223; Spectrum of early onset nephrotic syndrome associated with WT1 missense mutations.
Schumacher V.; Schaerer K.; Wuehl E.; Altrogge H.; Bonzel K.-E.; Guschmann M.; Neuhaus T.J.; Pollastro R.M.; Kuwertz-Broeking E.; Bulla M.; Tondera A.-M.; Mundel P.; Helmchen U.; Waldherr R.; Weirich A.; Royer-Pokora B.;
Kidney Int. 53:1594-1600(1998)
Cited for: VARIANTS NPHS4 LEU-364; HIS-366; CYS-379; ARG-385; GLN-394; TRP-394 AND ASN-396; Constitutional WT1 correlate with clinical features in children with progressive nephropathy.
Takata A.; Kikuchi H.; Fukuzawa R.; Ito S.; Honda M.; Hata J.;
J. Med. Genet. 37:698-701(2000)
Cited for: VARIANTS DDS ARG-342; TYR-355; HIS-366; ARG-385; PHE-388; TRP-394 AND ASN-396; VARIANT NPHS4 GLN-312; Twenty-four new cases of WT1 germline mutations and review of the literature: genotype/phenotype correlations for Wilms tumor development.
Royer-Pokora B.; Beier M.; Henzler M.; Alam R.; Schumacher V.; Weirich A.; Huff V.;
Am. J. Med. Genet. A 127:249-257(2004)
Cited for: VARIANTS WT1 SER-181; GLY-355; CYS-366; HIS-366; GLN-373; TRP-394 AND LEU-394; WT1 mutations in Meacham syndrome suggest a coelomic mesothelial origin of the cardiac and diaphragmatic malformations.
Suri M.; Kelehan P.; O'neill D.; Vadeyar S.; Grant J.; Ahmed S.F.; Tolmie J.; McCann E.; Lam W.; Smith S.; FitzPatrick D.; Hastie N.D.; Reardon W.;
Am. J. Med. Genet. A 143:2312-2320(2007)
Cited for: VARIANTS MEACHS CYS-366 AND TRP-394; Immunosuppression and renal outcome in congenital and pediatric steroid-resistant nephrotic syndrome.
Buescher A.K.; Kranz B.; Buescher R.; Hildebrandt F.; Dworniczak B.; Pennekamp P.; Kuwertz-Broeking E.; Wingen A.M.; John U.; Kemper M.; Monnens L.; Hoyer P.F.; Weber S.; Konrad M.;
Clin. J. Am. Soc. Nephrol. 5:2075-2084(2010)
Cited for: VARIANTS NPHS4 ARG-388; GLN-394; TRP-394 AND PRO-397;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.