UniProtKB/SwissProt variant VAR

Variant information

Variant position:

279

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 Tyrosine (Y) to Cysteine (C) at position 279 (Y279C, p.Tyr279Cys).

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 aromatic (Y) to medium size and polar (C)

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

BLOSUM score:

-2

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 NS1 and LPRD1; does not affect subcellular location; decreases protein tyrosine phosphatase activity against CDC73.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121918456 [ dbSNP | Ensembl ]

Sequence information

Variant position:

279

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

Protein sequence length:

593

The length of the canonical sequence.

Location on the sequence:

CKLLYSRKEGQRQENKNKNR Y KNILPFDHTRVVLHDGDPNE

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                         CKLLYSRKEGQRQENKNKNRYKNILPFDHTRVVLHDGDPNE

Mouse                         CKLLYSRKEGQRQENKNKNRYKNILPFDHTRVVLHDGDPNE

Rat                           CKLLYSRKEGQRQENKNKNRYKNILPFDHTRVVLHDGDPNE

Chicken                       CKLLYSRKEGQRQENKNKNRYKNILPFDHTRVVLHDGDPNE

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	2 – 593	Tyrosine-protein phosphatase non-receptor type 11
Domain	247 – 517	Tyrosine-protein phosphatase
Beta strand	277 – 279

Literature citations

PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity.
Tartaglia M.; Kalidas K.; Shaw A.; Song X.; Musat D.L.; van der Burgt I.; Brunner H.G.; Bertola D.R.; Crosby A.H.; Ion A.; Kucherlapati R.S.; Jeffery S.; Patton M.A.; Gelb B.D.;
Am. J. Hum. Genet. 70:1555-1563(2002)
Cited for: VARIANTS NS1 ALA-42; ALA-60; ASN-61; GLY-61; ASP-62; CYS-63; GLY-72; ILE-73; ASP-76; ARG-79; ALA-106; ASP-139; CYS-279; VAL-282; LEU-285; SER-285; ASP-308; SER-308; VAL-309; LYS-501 AND VAL-504;

Grouping of multiple-lentigines/LEOPARD and Noonan syndromes on the PTPN11 gene.
Digilio M.C.; Conti E.; Sarkozy A.; Mingarelli R.; Dottorini T.; Marino B.; Pizzuti A.; Dallapiccola B.;
Am. J. Hum. Genet. 71:389-394(2002)
Cited for: VARIANTS LPRD1 CYS-279 AND MET-468;

Correlation between PTPN11 gene mutations and congenital heart defects in Noonan and LEOPARD syndromes.
Sarkozy A.; Conti E.; Seripa D.; Digilio M.C.; Grifone N.; Tandoi C.; Fazio V.M.; Di Ciommo V.; Marino B.; Pizzuti A.; Dallapiccola B.;
J. Med. Genet. 40:704-708(2003)
Cited for: VARIANTS NS1 ILE-2; ALA-42; ASP-62; CYS-63; GLY-72; PRO-79; ALA-106; CYS-279; ASP-308; SER-308; MET-468; ARG-503; VAL-504 AND PHE-560;

PTPN11 mutations in patients with LEOPARD syndrome: a French multicentric experience.
Keren B.; Hadchouel A.; Saba S.; Sznajer Y.; Bonneau D.; Leheup B.; Boute O.; Gaillard D.; Lacombe D.; Layet V.; Marlin S.; Mortier G.; Toutain A.; Beylot C.; Baumann C.; Verloes A.; Cave H.;
J. Med. Genet. 41:E117-E117(2004)
Cited for: VARIANTS LPRD1 CYS-279; SER-279; MET-468 AND PRO-510;

Clinical and molecular analysis of 30 patients with multiple lentigines LEOPARD syndrome.
Sarkozy A.; Conti E.; Digilio M.C.; Marino B.; Morini E.; Pacileo G.; Wilson M.; Calabro R.; Pizzuti A.; Dallapiccola B.;
J. Med. Genet. 41:E68-E68(2004)
Cited for: VARIANTS LPRD1 CYS-279; SER-279; ALA-464; MET-468; TRP-498; LEU-498 AND PRO-506;

Acute myelomonocytic leukemia in a boy with LEOPARD syndrome (PTPN11 gene mutation positive).
Ucar C.; Calyskan U.; Martini S.; Heinritz W.;
J. Pediatr. Hematol. Oncol. 28:123-125(2006)
Cited for: VARIANT LPRD1 CYS-279;

Determination of the catalytic activity of LEOPARD syndrome-associated SHP2 mutants toward parafibromin, a bona fide SHP2 substrate involved in Wnt signaling.
Noda S.; Takahashi A.; Hayashi T.; Tanuma S.; Hatakeyama M.;
Biochem. Biophys. Res. Commun. 469:1133-1139(2016)
Cited for: VARIANT JMML LYS-76; CHARACTERIZATION OF VARIANT JMML LYS-76; VARIANTS LPRD1 CYS-279; MET-468; PRO-506 AND GLU-510; CHARACTERIZATION OF VARIANTS LPRD1 CYS-279; MET-468; PRO-506 AND GLU-510; FUNCTION; CATALYTIC ACTIVITY; INTERACTION WITH CDC73; SUBCELLULAR LOCATION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q06124: Variant p.Tyr279Cys