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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q96RR1: Variant p.Arg303Trp

Twinkle mtDNA helicase
Gene: TWNK
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Variant information Variant position: help 303 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 Arginine (R) to Tryptophan (W) at position 303 (R303W, p.Arg303Trp). 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 Change from large size and basic (R) to large size and aromatic (W) 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 PEOA3; also detected in a case showing digenic inheritance. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 303 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 684 The length of the canonical sequence.
Location on the sequence: help LPRGTTCLPPALLPYLEQFR R IVFWLGDDLRSWEAAKLFAR 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                         LPRGTTCLPPALLPYLEQFRRIVFWLG-DDLRSWEAAKLFAR

Mouse                         LPRGTVCLPPALLPYLEQFRRIVFWLG-DDLRSWEAAKLFA

Chicken                       LPRGATILPPALLPYLEQFRRVTLWLG-DDLRSWEASKLFA

Drosophila                    LPYELKTLPQECLPALERFKELIFWLHYDASHSWDAARAFA
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 32 – 684 Twinkle mtDNA helicase
Region 121 – 372 Required for hexamers formation and DNA helicase activity
Region 215 – 335 Primase-like domain



Literature citations
Mutations of ANT1, Twinkle, and POLG1 in sporadic progressive external ophthalmoplegia (PEO).
Agostino A.; Valletta L.; Chinnery P.F.; Ferrari G.; Carrara F.; Taylor R.W.; Schaefer A.M.; Turnbull D.M.; Tiranti V.; Zeviani M.;
Neurology 60:1354-1356(2003)
Cited for: VARIANTS PEO TRP-303 AND GLN-334; Novel Twinkle (PEO1) gene mutations in Mendelian progressive external ophthalmoplegia.
Virgilio R.; Ronchi D.; Hadjigeorgiou G.M.; Bordoni A.; Saladino F.; Moggio M.; Adobbati L.; Kafetsouli D.; Tsironi E.; Previtali S.; Papadimitriou A.; Bresolin N.; Comi G.P.;
J. Neurol. 255:1384-1391(2008)
Cited for: VARIANTS PEOA3 TRP-303; SER-315; PRO-334; ASN-426; SER-474; ILE-478 AND LYS-479; Molecular analysis in a family presenting with a mild form of late-onset autosomal dominant chronic progressive external ophthalmoplegia.
Negro R.; Zoccolella S.; Dell'aglio R.; Amati A.; Artuso L.; Bisceglia L.; Lavolpe V.; Papa S.; Serlenga L.; Petruzzella V.;
Neuromuscul. Disord. 19:423-426(2009)
Cited for: VARIANT PEOA3 TRP-303; The clinical, histochemical, and molecular spectrum of PEO1 (Twinkle)-linked adPEO.
Fratter C.; Gorman G.S.; Stewart J.D.; Buddles M.; Smith C.; Evans J.; Seller A.; Poulton J.; Roberts M.; Hanna M.G.; Rahman S.; Omer S.E.; Klopstock T.; Schoser B.; Kornblum C.; Czermin B.; Lecky B.; Blakely E.L.; Craig K.; Chinnery P.F.; Turnbull D.M.; Horvath R.; Taylor R.W.;
Neurology 74:1619-1626(2010)
Cited for: VARIANTS PEOA3 GLN-303; TRP-303; GLN-334; PRO-354; PRO-357; THR-359; PRO-362; LEU-363; CYS-370; GLN-374; PRO-381; HIS-458; PRO-460; ASP-475 AND LYS-479;
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.