UniProtKB/SwissProt variant VAR

Variant information

Variant position:

613

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 Leucine (L) to Valine (V) at position 613 (L613V, p.Leu613Val).

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:

Similar physico-chemical property. Both residues are medium size and hydrophobic.

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 NS5 and LPRD2; shows in vitro greater kinase activity and enhanced MAPK1 activation than wild-type.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs80338797 [ dbSNP | Ensembl ]

Sequence information

Variant position:

613

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

Protein sequence length:

648

The length of the canonical sequence.

Location on the sequence:

KEERPLFPQILSSIELLQHS L PKINRSASEPSLHRAAHTED

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                         KEERPLFPQILSSIELLQHSLPKINRSASEPSLHRAAHTED

Mouse                         KEERPLFPQILSSIELLQHSLPKINRSASEPSLHRAAHTED

Rat                           KEERPLFPQILSSIELLQHSLPKINRSASEPSLHRAAHTED

Bovine                        KEERPLFPQILSSIELLQHSLPKINRSASEPSLHRAAHTED

Chicken                       REERPLFPQILSSIELLQHSLPKINRSASEPSLHRASHTED

Xenopus laevis                RDERPLFPQILSSIELLQHSLPKINRSALEPSLHRAAHTED

Fission yeast                 GEFRIIENRLLT-----------------------------

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 – 648	RAF proto-oncogene serine/threonine-protein kinase
Modified residue	621 – 621	Phosphoserine

Literature citations

Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy.
Pandit B.; Sarkozy A.; Pennacchio L.A.; Carta C.; Oishi K.; Martinelli S.; Pogna E.A.; Schackwitz W.; Ustaszewska A.; Landstrom A.; Bos J.M.; Ommen S.R.; Esposito G.; Lepri F.; Faul C.; Mundel P.; Lopez Siguero J.P.; Tenconi R.; Selicorni A.; Rossi C.; Mazzanti L.; Torrente I.; Marino B.; Digilio M.C.; Zampino G.; Ackerman M.J.; Dallapiccola B.; Tartaglia M.; Gelb B.D.;
Nat. Genet. 39:1007-1012(2007)
Cited for: VARIANTS NS5 SER-256; PHE-259; ARG-260; LEU-261; SER-261; ASN-486; GLY-486; ILE-491; ARG-491 AND THR-612; VARIANT HYPERTROPHIC CARDIOMYOPATHY ILE-260; VARIANTS LPRD2 LEU-257 AND VAL-613; VARIANT NS5 LEU-257; CHARACTERIZATION OF VARIANTS NS5 SER-261; ASN-486 AND ILE-491; CHARACTERIZATION OF VARIANT LPRD2 VAL-613; CATALYTIC ACTIVITY;

Germline gain-of-function mutations in RAF1 cause Noonan syndrome.
Razzaque M.A.; Nishizawa T.; Komoike Y.; Yagi H.; Furutani M.; Amo R.; Kamisago M.; Momma K.; Katayama H.; Nakagawa M.; Fujiwara Y.; Matsushima M.; Mizuno K.; Tokuyama M.; Hirota H.; Muneuchi J.; Higashinakagawa T.; Matsuoka R.;
Nat. Genet. 39:1013-1017(2007)
Cited for: VARIANTS NS5 LEU-257; ALA-261; SER-261; ALA-263 AND VAL-613; CHARACTERIZATION OF VARIANTS NS5 LEU-257; ALA-261; SER-261; ALA-263 AND VAL-613;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P04049: Variant p.Leu613Val