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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P54098: Variant p.Thr251Ile

DNA polymerase subunit gamma-1
Gene: POLG
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Variant information Variant position: help 251 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 Threonine (T) to Isoleucine (I) at position 251 (T251I, p.Thr251Ile). 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 medium size and polar (T) to medium size and hydrophobic (I) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In PEOB1, MTDPS4A and MTDPS4B. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 251 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 1239 The length of the canonical sequence.
Location on the sequence: help ERYSWTSQLSPADLIPLEVP T GASSPTQRDWQEQLVVGHNV 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                         ERYSWTSQLSPADLIPLEVPTGASSPTQRDWQ--------EQLVVGHNV

Mouse                         ERYSWTSQLSPADLIPLGGSTSASSSTKQDGQ--------E

Rat                           ERYSWTSQLSPADLIPLGVSASASSSTQQDWQ--------E

Xenopus laevis                GRYTWSKELLLSDLFPLETSMNCNYMTKNNWT--------E

Drosophila                    HR------LSVEKLEPLDVDTDSERPHYTTDELIPLGTTGP
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 – 1239 DNA polymerase subunit gamma-1
Helix 248 – 251



Literature citations
Mutations of mitochondrial DNA polymerase gammaA are a frequent cause of autosomal dominant or recessive progressive external ophthalmoplegia.
Lamantea E.; Tiranti V.; Bordoni A.; Toscano A.; Bono F.; Servidei S.; Papadimitriou A.; Spelbrink H.; Silvestri L.; Casari G.; Comi G.P.; Zeviani M.;
Ann. Neurol. 52:211-219(2002)
Cited for: VARIANTS PEOA1 ASP-923; HIS-943; CYS-955; SER-957 AND LEU-1176; VARIANTS PEOB1 ILE-251; LEU-309 AND SER-848; Novel POLG mutations in progressive external ophthalmoplegia mimicking mitochondrial neurogastrointestinal encephalomyopathy.
Van Goethem G.; Schwartz M.; Loefgren A.; Dermaut B.; Van Broeckhoven C.; Vissing J.;
Eur. J. Hum. Genet. 11:547-549(2003)
Cited for: VARIANTS MTDPS4B ILE-251; LEU-587 AND SER-864; POLG mutations in sporadic mitochondrial disorders with multiple mtDNA deletions.
Di Fonzo A.; Bordoni A.; Crimi M.; Sara G.; Del Bo R.; Bresolin N.; Comi G.P.;
Hum. Mutat. 22:498-499(2003)
Cited for: VARIANTS PEOB1 ILE-251; ALA-268; ARG-312; THR-467; GLN-562; LEU-587; PRO-807 AND TYR-932; VARIANTS GLY-1143 AND HIS-1236; 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 PEOB1 TRP-227; ILE-251; ARG-312; VAL-431; THR-467; GLN-1047; CYS-1096 AND CYS-1104; Sequence analysis of familial PEO shows additional mutations associated with the 752C-->T and 3527C-->T changes in the POLG1 gene.
Lamantea E.; Zeviani M.;
Ann. Neurol. 56:454-455(2004)
Cited for: VARIANTS PEOB1 TRP-227; ILE-251; LEU-309; LEU-587; SER-848; ILE-1106 AND LEU-1176; Infantile hepatocerebral syndromes associated with mutations in the mitochondrial DNA polymerase-gammaA.
Ferrari G.; Lamantea E.; Donati A.; Filosto M.; Briem E.; Carrara F.; Parini R.; Simonati A.; Santer R.; Zeviani M.;
Brain 128:723-731(2005)
Cited for: VARIANTS MTDPS4A GLY-232; PRO-244; ILE-251; THR-467; LEU-587; SER-748; SER-848 AND PRO-957; VARIANT GLY-1143; Analysis of mutant DNA polymerase gamma in patients with mitochondrial DNA depletion.
Taanman J.-W.; Rahman S.; Pagnamenta A.T.; Morris A.A.M.; Bitner-Glindzicz M.; Wolf N.I.; Leonard J.V.; Clayton P.T.; Schapira A.H.V.;
Hum. Mutat. 30:248-254(2009)
Cited for: VARIANTS LS HIS-232 AND SER-848; VARIANTS MTDPS4A ILE-251; THR-467; LEU-587; SER-748; CYS-831; SER-848; PRO-914; TYR-1110; ARG-1134 AND LYS-1136; VARIANTS GLY-1143 AND HIS-1236;
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.