UniProtKB/Swiss-Prot P54098: Variant p.Gly848Ser

DNA polymerase subunit gamma-1
Gene: POLG
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Variant information Variant position:

848 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 Glycine (G) to Serine (S) at position 848 (G848S, p.Gly848Ser). 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 glycine (G) to small size and polar (S) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

0 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 PEOB1, MTDPS4A, MTDPS4B and LS; also found in a patient with epileptic encephalopathy, developmental delay and moderate intellectual disability. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs113994098 [ dbSNP | Ensembl ]

Sequence information Variant position:

848 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

1239 The length of the canonical sequence.
Location on the sequence:

HPDYDEEGLYGAILPQVVTA G TITRRAVEPTWLTASNARPD 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                         HPDYDEEGLYGAILPQVVTAGTITRRAVEPTWLTASNARPD

Mouse                         HPAFDEEGHYGAILPQVVTAGTITRRAVEPTWLTASNARPD

Rat                           HPSFDEESHYGAILPQVVTAGTITRRAVEPTWLTASNARPD

Xenopus laevis                DPEFDEENKYGAILAQVVSAGTITRRAVEPTWLTASNARAD

Drosophila                    EKC--QPIAYGAICPQVVACGTLTRRAMEPTWMTASNSRPD

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 – 1239	DNA polymerase subunit gamma-1
Binding site	849 – 849
Binding site	863 – 863
Site	853 – 853	Critical for replication fidelity and mismatch recognition
Mutagenesis	853 – 853	R -> A. Abolishes primer DNA extention in the presence of dNTPs. Impairs intrinsic polymerase processivity. Enhances exonuclease activity leading to primer DNA degradation.
Beta strand	845 – 848

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; Digenic progressive external ophthalmoplegia in a sporadic patient: recessive mutations in POLG and C10orf2/Twinkle.
Van Goethem G.; Loefgren A.; Dermaut B.; Ceuterick C.; Martin J.-J.; Van Broeckhoven C.;
Hum. Mutat. 22:175-176(2003)
Cited for: VARIANT PEOB1 SER-848; 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; POLG mutations and Alpers syndrome.
Davidzon G.; Mancuso M.; Ferraris S.; Quinzii C.; Hirano M.; Peters H.L.; Kirby D.; Thorburn D.R.; DiMauro S.;
Ann. Neurol. 57:921-923(2005)
Cited for: VARIANTS MTDPS4A SER-748 AND SER-848; 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; Fatal congenital myopathy and gastrointestinal pseudo-obstruction due to POLG1 mutations.
Giordano C.; Powell H.; Leopizzi M.; de Curtis M.; Travaglini C.; Sebastiani M.; Gallo P.; Taylor R.W.; d'Amati G.;
Neurology 72:1103-1105(2009)
Cited for: VARIANTS MTDPS4B TRP-227 AND SER-848; Localized cerebral energy failure in DNA polymerase gamma-associated encephalopathy syndromes.
Tzoulis C.; Neckelmann G.; Moerk S.J.; Engelsen B.E.; Viscomi C.; Moen G.; Ersland L.; Zeviani M.; Bindoff L.A.;
Brain 133:1428-1437(2010)
Cited for: VARIANTS SCAE THR-467 AND SER-748; VARIANTS MTDPS4A ARG-303; THR-467 AND SER-848; Alpers syndrome with mutations in POLG: clinical and investigative features.
Hunter M.F.; Peters H.; Salemi R.; Thorburn D.; Mackay M.T.;
Pediatr. Neurol. 45:311-318(2011)
Cited for: VARIANTS MTDPS4A ARG-305; THR-467; SER-748; SER-848; CYS-852 AND ARG-966; The role of recessive inheritance in early-onset epileptic encephalopathies: a combined whole-exome sequencing and copy number study.
Papuc S.M.; Abela L.; Steindl K.; Begemann A.; Simmons T.L.; Schmitt B.; Zweier M.; Oneda B.; Socher E.; Crowther L.M.; Wohlrab G.; Gogoll L.; Poms M.; Seiler M.; Papik M.; Baldinger R.; Baumer A.; Asadollahi R.; Kroell-Seger J.; Schmid R.; Iff T.; Schmitt-Mechelke T.; Otten K.; Hackenberg A.; Addor M.C.; Klein A.; Azzarello-Burri S.; Sticht H.; Joset P.; Plecko B.; Rauch A.;
Eur. J. Hum. Genet. 27:408-421(2019)
Cited for: VARIANTS GLN-275 AND SER-848;

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.