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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P41250: Variant p.Ile334Phe

Glycine--tRNA ligase
Gene: GARS1
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Variant information Variant position: help 334 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help US 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 Isoleucine (I) to Phenylalanine (F) at position 334 (I334F, p.Ile334Phe). 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 hydrophobic (I) to large size and aromatic (F) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 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: help In CMT2D; uncertain significance; shows a large reduction in aminoacylation activity; demonstrates a change in subcellular location pattern; does not associate with granules. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 334 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 739 The length of the canonical sequence.
Location on the sequence: help FNQGKLPFAAAQIGNSFRNE I SPRSGLIRVREFTMAEIEHF 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                         FNQGKLPFAAAQIGNSFRNEISPRSGLIRVREFTMAEIEHF

Mouse                         FNQGKLPFAAAQIGNSFRNEISPRSGLIRVREFTMAEIEHF

Rat                           FNQGKLPFAAAQIGNSFRNEISPRSGLIRVREFTMAEIEHF

Caenorhabditis elegans        FNQGKLPFAAAQIGLGFRNEISPRQGLIRVREFTMCEIEHF

Drosophila                    FNQGKLPFAVAQIGNSFRNEISPRSGLIRVREFTMAEIEHF

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 37 – 739 Glycine--tRNA ligase
Binding site 350 – 350
Mutagenesis 337 – 337 R -> A. Decrease in catalytic activity by more than 10-fold.



Literature citations
Impaired function is a common feature of neuropathy-associated glycyl-tRNA synthetase mutations.
Griffin L.B.; Sakaguchi R.; McGuigan D.; Gonzalez M.A.; Searby C.; Zuchner S.; Hou Y.M.; Antonellis A.;
Hum. Mutat. 35:1363-1371(2014)
Cited for: SUBCELLULAR LOCATION (ISOFORM 2); VARIANTS CMT2D VAL-111; ASN-200; PHE-265; ARG-294; LEU-298; PHE-334; ARG-472; ASN-554; ARG-580 AND ALA-652; VARIANT LEU-635; CHARACTERIZATION OF VARIANTS CMT2D VAL-111; GLY-125; PRO-183; ASN-200; PHE-265; ARG-294; LEU-298; PHE-334; ARG-472; ASN-554; ARG-580 AND ALA-652; CHARACTERIZATION OF VARIANT LEU-635; Severe childhood SMA and axonal CMT due to anticodon binding domain mutations in the GARS gene.
James P.A.; Cader M.Z.; Muntoni F.; Childs A.M.; Crow Y.J.; Talbot K.;
Neurology 67:1710-1712(2006)
Cited for: VARIANT LEU-635; VARIANTS CMT2D PHE-334 AND ALA-652; Application of whole exome sequencing in undiagnosed inherited polyneuropathies.
Klein C.J.; Middha S.; Duan X.; Wu Y.; Litchy W.J.; Gu W.; Dyck P.J.; Gavrilova R.H.; Smith D.I.; Kocher J.P.; Dyck P.J.;
J. Neurol. Neurosurg. Psych. 85:1265-1272(2014)
Cited for: VARIANT CMT2D PHE-334;
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.