UniProtKB/Swiss-Prot Q92963: Variant p.Thr83Pro

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 83 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LB/B 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 Proline (P) at position 83 (T83P, p.Thr83Pro). 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 (P) 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 patients with features of Noonan syndrome; likely pathogenic. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs869025195 [ dbSNP | Ensembl ]

Sequence information

Variant position: 83 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 219 The length of the canonical sequence.
Location on the sequence: RIDDEPANLDILDTAGQAEF T AMRDQYMRAGEGFIICYSIT 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.
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 – 219	GTP-binding protein Rit1
Mutagenesis	79 – 79	Q -> L. Constitutively active. Dramatic reduction of the rate of GTP hydrolysis. Loss of interaction with AFDN, RLF and RALGDS; when associated with S-53. Loss of interaction with AFDN; when associated with G-55.

Literature citations

Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome.
Aoki Y.; Niihori T.; Banjo T.; Okamoto N.; Mizuno S.; Kurosawa K.; Ogata T.; Takada F.; Yano M.; Ando T.; Hoshika T.; Barnett C.; Ohashi H.; Kawame H.; Hasegawa T.; Okutani T.; Nagashima T.; Hasegawa S.; Funayama R.; Nagashima T.; Nakayama K.; Inoue S.; Watanabe Y.; Ogura T.; Matsubara Y.;
Am. J. Hum. Genet. 93:173-180(2013)
Cited for: FUNCTION; INVOLVEMENT IN NS8; VARIANTS NS8 GLY-57; GLY-81; LEU-82; ILE-90 AND ALA-95; CHARACTERIZATION OF VARIANTS NS8 GLY-57; GLY-81; LEU-82; ILE-90 AND ALA-95; VARIANTS THR-35; VAL-82; PRO-83 AND HIS-89;