UniProtKB/Swiss-Prot O43776: Variant p.Leu350Pro

Asparagine--tRNA ligase, cytoplasmic
Gene: NARS1
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Variant information Variant position:

350 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

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:

From Leucine (L) to Proline (P) at position 350 (L350P, p.Leu350Pro). 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:

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:

-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:

In NEDMILG; uncertain significance. Any additional useful information about the variant.

Sequence information Variant position:

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

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

RHLAEYTHVEAECPFLTFDD L LNRLEDLVCDVVDRILKSPA 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                         RHLAEYTHVEAECPFLTFDDLLNRLEDLVCDVVDRILK-SP-A

Mouse                         RHLAEFTHVEAECPFLTFEDLLNRLEDLVCDVVDRVLK-SP

Bovine                        RHLAEYTHVEAECPFLTFEELLNRLEDLVCDVVDRVLK-SP

Caenorhabditis elegans        RHLSEYQHVEAECAFITFDQLMDRIEALVCDTVDRLLA-DP

Slime mold                    RHLTEFLHLEAECPFITYEELQDRIEFLVVDVCEKLFKMDP

Baker's yeast                 RHLSEYTHIEAELAFLTFDDLLQHIETLIVKSVQYVLE-DP

Fission yeast                 RHLSEFTHVEFELPFVNFGEFLEIIEEFICQTIDRLLD-DP

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 – 548	Asparagine--tRNA ligase, cytoplasmic
Alternative sequence	174 – 547	Missing. In isoform 2.
Helix	347 – 367

Literature citations
De novo and bi-allelic pathogenic variants in NARS1 cause neurodevelopmental delay due to toxic gain-of-function and partial loss-of-function effects.
Manole A.; Efthymiou S.; O'Connor E.; Mendes M.I.; Jennings M.; Maroofian R.; Davagnanam I.; Mankad K.; Lopez M.R.; Salpietro V.; Harripaul R.; Badalato L.; Walia J.; Francklyn C.S.; Athanasiou-Fragkouli A.; Sullivan R.; Desai S.; Baranano K.; Zafar F.; Rana N.; Ilyas M.; Horga A.; Kara M.; Mattioli F.; Goldenberg A.; Griffin H.; Piton A.; Henderson L.B.; Kara B.; Aslanger A.D.; Raaphorst J.; Pfundt R.; Portier R.; Shinawi M.; Kirby A.; Christensen K.M.; Wang L.; Rosti R.O.; Paracha S.A.; Sarwar M.T.; Jenkins D.; Ahmed J.; Santoni F.A.; Ranza E.; Iwaszkiewicz J.; Cytrynbaum C.; Weksberg R.; Wentzensen I.M.; Guillen Sacoto M.J.; Si Y.; Telegrafi A.; Andrews M.V.; Baldridge D.; Gabriel H.; Mohr J.; Oehl-Jaschkowitz B.; Debard S.; Senger B.; Fischer F.; van Ravenwaaij C.; Fock A.J.M.; Stevens S.J.C.; Baehler J.; Nasar A.; Mantovani J.F.; Manzur A.; Sarkozy A.; Smith D.E.C.; Salomons G.S.; Ahmed Z.M.; Riazuddin S.; Riazuddin S.; Usmani M.A.; Seibt A.; Ansar M.; Antonarakis S.E.; Vincent J.B.; Ayub M.; Grimmel M.; Jelsig A.M.; Hjortshoej T.D.; Karstensen H.G.; Hummel M.; Haack T.B.; Jamshidi Y.; Distelmaier F.; Horvath R.; Gleeson J.G.; Becker H.; Mandel J.L.; Koolen D.A.; Houlden H.;
Am. J. Hum. Genet. 107:311-324(2020)
Cited for: VARIANTS NEDMILG PRO-11; MET-17; GLU-60; 90-ARG--PRO-548 DEL; CYS-132; PRO-350; ALA-356; THR-422; ILE-459 AND CYS-545; VARIANTS NEDMILEG LEU-322; SER-509 AND 534-ARG--PRO-548 DEL; INVOLVEMENT IN NEDMILG; INVOLVEMENT IN NEDMILEG; CHARACTERIZATION OF VARIANT NEDMILG PRO-11; CHARACTERIZATION OF VARIANTS NEDMILEG LEU-322 AND 534-ARG--PRO-548 DEL; FUNCTION; CATALYTIC ACTIVITY;

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.