UniProtKB/SwissProt variant VAR

Variant information

Variant position:

1444

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 Lysine (K) to Glutamate (E) at position 1444 (K1444E, p.Lys1444Glu).

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 (K) to medium size and acidic (E)

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:

In NF1 and NFNS; significant reduction of intrinsic GAP activity.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs137854550 [ dbSNP | Ensembl ]

Sequence information

Variant position:

1444

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

Protein sequence length:

2839

The length of the canonical sequence.

Location on the sequence:

AGILDKKPPPRIERGLKLMS K ILQSIANHVLFTKEEHMRPF

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                         AGILDKKPPPRIERGLKLMSKILQSIANHVLFTKEEHMRPF

Mouse                         AGILDKKPPPRIERGLKLMSKVLQSIANHVLFTKEEHMRPF

Rat                           AGILDKKPPPRIERGLKLMSKVLQSIANHVLFTKEEHMRPF

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 – 2839	Neurofibromin
Domain	1235 – 1451	Ras-GAP
Alternative sequence	552 – 2839	Missing. In isoform 3.
Alternative sequence	594 – 2839	Missing. In isoform 5.
Helix	1433 – 1451

Literature citations

Somatic mutations in the neurofibromatosis 1 gene in human tumors.
Li Y.; Bollag G.; Clark R.; Stevens J.; Conroy L.; Fults D.; Ward K.; Friedman E.; Samowitz W.; Robertson M.; Bradley P.; McCormick F.; White R.; Cawthon R.M.;
Cell 69:275-281(1992)
Cited for: VARIANT GLU-1444;

Mutational and functional analysis of the neurofibromatosis type 1 (NF1) gene.
Upadhyaya M.; Osborn M.J.; Maynard J.; Kim M.R.; Tamanoi F.; Cooper D.N.;
Hum. Genet. 99:88-92(1997)
Cited for: VARIANTS NF1 SER-1412; GLN-1440; GLU-1444 AND GLY-1489;

NF1 mutations in neurofibromatosis 1 patients with plexiform neurofibromas.
Kluwe L.; Friedrich R.E.; Korf B.; Fahsold R.; Mautner V.-F.;
Hum. Mutat. 19:309-309(2002)
Cited for: VARIANTS NF1 PHE-82; ARG-784 AND GLU-1444;

NF1 gene mutations represent the major molecular event underlying neurofibromatosis-Noonan syndrome.
De Luca A.; Bottillo I.; Sarkozy A.; Carta C.; Neri C.; Bellacchio E.; Schirinzi A.; Conti E.; Zampino G.; Battaglia A.; Majore S.; Rinaldi M.M.; Carella M.; Marino B.; Pizzuti A.; Digilio M.C.; Tartaglia M.; Dallapiccola B.;
Am. J. Hum. Genet. 77:1092-1101(2005)
Cited for: VARIANTS NFNS ARG-194; GLU-1444; THR-1451; LEU-1453 AND GLU-1459 DEL;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P21359: Variant p.Lys1444Glu