UniProtKB/SwissProt variant VAR

Variant information

Variant position:

1346

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:

US

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 Threonine (T) to Methionine (M) at position 1346 (T1346M, p.Thr1346Met).

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 medium size and polar (T) to medium size and hydrophobic (M)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-1

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:

Found in a patient with severe intellectual disability, behavioral problems, microcephaly, congenital cardiac defect and herniation of the abdominal diaphragm; also observed in some colorectal cancers; reduced phosphatase activity; unknown pathological significance.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs199947379 [ dbSNP | Ensembl ]

Sequence information

Variant position:

1346

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:

1441

The length of the canonical sequence.

Location on the sequence:

QDGYRIVQHLQYIGWPAYRD T PPSKRSLLKVVRRLEKWQEQ

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                         QDGYRIVQHLQYIGWPAYRDTPPSKRSLLKVVRRLEKWQEQ

Mouse                         QDGYRIVQHLQYIGWPAYRDTPPSKRSLLKVVRRLEKWQEQ

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	26 – 1441	Receptor-type tyrosine-protein phosphatase T
Topological domain	769 – 1441	Cytoplasmic
Domain	1175 – 1437	Tyrosine-protein phosphatase 2

Literature citations

Mutational analysis of the tyrosine phosphatome in colorectal cancers.
Wang Z.; Shen D.; Parsons D.W.; Bardelli A.; Sager J.; Szabo S.; Ptak J.; Silliman N.; Peters B.A.; van der Heijden M.S.; Parmigiani G.; Yan H.; Wang T.-L.; Riggins G.; Powell S.M.; Willson J.K.V.; Markowitz S.; Kinzler K.W.; Vogelstein B.; Velculescu V.E.;
Science 304:1164-1166(2004)
Cited for: VARIANTS SER-74; THR-209; THR-218; SER-248; HIS-280; VAL-395; PHE-412; CYS-453; LYS-510; MET-605; GLY-648; THR-707; VAL-707; PRO-708; ILE-771; GLY-905; LYS-965; PRO-1096; ILE-1106; TRP-1190; LEU-1237; MET-1247; LEU-1324; PHE-1329 AND MET-1346; TISSUE SPECIFICITY;

Identification of pathogenic gene variants in small families with intellectually disabled siblings by exome sequencing.
Schuurs-Hoeijmakers J.H.; Vulto-van Silfhout A.T.; Vissers L.E.; van de Vondervoort I.I.; van Bon B.W.; de Ligt J.; Gilissen C.; Hehir-Kwa J.Y.; Neveling K.; del Rosario M.; Hira G.; Reitano S.; Vitello A.; Failla P.; Greco D.; Fichera M.; Galesi O.; Kleefstra T.; Greally M.T.; Ockeloen C.W.; Willemsen M.H.; Bongers E.M.; Janssen I.M.; Pfundt R.; Veltman J.A.; Romano C.; Willemsen M.A.; van Bokhoven H.; Brunner H.G.; de Vries B.B.; de Brouwer A.P.;
J. Med. Genet. 50:802-811(2013)
Cited for: VARIANT MET-1346;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O14522: Variant p.Thr1346Met