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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P49815: Variant p.Pro1675Leu

Tuberin
Gene: TSC2
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Variant information Variant position: help 1675 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Proline (P) to Leucine (L) at position 1675 (P1675L, p.Pro1675Leu). 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: help 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: help -3 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: help In TSC2. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 1675 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 1807 The length of the canonical sequence.
Location on the sequence: help EDFKLGTIKGQFNFVHVIVT P LDYECNLVSLQCRKDMEGLV 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         EDFKLGTIK-GQFNFVHVIVTPLDYECNLVSLQCRKD----------MEGL----V

Mouse                         EDFKLGTIKQGQFNFVHVIITPLDYKCNLLTLQCRKDGPAC

Rat                           EDFKLGTIK-GQFNFVHVIITPLDYKCNLLTLQCRKD----

Fission yeast                 LEYDFDTIP-SQFNFVNIVITPESESIRRTGRQIK------
Sequence annotation in neighborhood: help 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.
TypePositionsDescription
Chain 1 – 1807 Tuberin
Domain 1531 – 1758 Rap-GAP
Alternative sequence 240 – 1807 Missing. In isoform 8.
Mutagenesis 1666 – 1666 F -> A. Decreased GTPase-activating protein activity.



Literature citations
The GAP-related domain of tuberin, the product of the TSC2 gene, is a target for missense mutations in tuberous sclerosis.
Maheshwar M.M.; Cheadle J.P.; Jones A.C.; Myring J.; Fryer A.E.; Harris P.C.; Sampson J.R.;
Hum. Mol. Genet. 6:1991-1996(1997)
Cited for: VARIANTS TSC2 PHE-1509 DEL; MET-1594; LYS-1643; SER-1651; LEU-1675 AND LYS-1681; Comprehensive mutation analysis of TSC1 and TSC2- and phenotypic correlations in 150 families with tuberous sclerosis.
Jones A.C.; Shyamsundar M.M.; Thomas M.W.; Maynard J.; Idziaszczyk S.A.; Tomkins S.; Sampson J.R.; Cheadle J.P.;
Am. J. Hum. Genet. 64:1305-1315(1999)
Cited for: VARIANTS TSC2 GLU-294; GLN-611; TRP-611; ASP-614; TYR-696; TRP-905; ARG-1497; ASN-1498; MET-1594; LYS-1643; SER-1651; LEU-1675; LYS-1681 AND PRO-1743; Analysis of both TSC1 and TSC2 for germline mutations in 126 unrelated patients with tuberous sclerosis.
Niida Y.; Lawrence-Smith N.; Banwell A.; Hammer E.; Lewis J.; Beauchamp R.L.; Sims K.; Ramesh V.; Ozelius L.;
Hum. Mutat. 14:412-422(1999)
Cited for: VARIANTS TSC2 SER-525; MET-599; GLN-611; VAL-895; TYR-1620; LEU-1675 AND THR-1704; Mutational analysis of TSC1 and TSC2 genes in Japanese patients with tuberous sclerosis complex.
Zhang H.; Nanba E.; Yamamoto T.; Ninomiya H.; Ohno K.; Mizuguchi M.; Takeshita K.;
J. Hum. Genet. 44:391-396(1999)
Cited for: VARIANTS TSC2 ARG-137; PHE-320; GLN-611; ASN-647; ARG-717; GLU-769; MET-963 AND LEU-1675; INVOLVEMENT IN TSC2; Novel TSC2 mutations and decreased expression of tuberin in cultured tumor cells with an insertion mutation.
Feng J.-H.; Yamamoto T.; Nanba E.; Ninomiya H.; Oka A.; Ohno K.;
Hum. Mutat. 23:397-397(2004)
Cited for: VARIANTS TSC2 SER-1651; PHE-1653; LEU-1675 AND 1746-HIS--ARG-1751 DEL; VARIANTS THR-607; VAL-862; SER-1429 AND ARG-1450;
Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.