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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O14746: Variant p.His412Tyr

Telomerase reverse transcriptase
Gene: TERT
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Variant information Variant position: help 412 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 Histidine (H) to Tyrosine (Y) at position 412 (H412Y, p.His412Tyr). 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 (H) to large size and aromatic (Y) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 2 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 PFBMFT1, AA and DKCB4; severe and moderate; risk factor for acute myelogenous leukemia; the mutant protein has 36% residual activity. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 412 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 1132 The length of the canonical sequence.
Location on the sequence: help LFLELLGNHAQCPYGVLLKT H CPLRAAVTPAAGVCAREKPQ 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                         LFLELLGNHAQCPYGVLLKTHCPLRAAVT---------PAAGVCAREKPQ

                              LFQELLGNHARCPYRALLRTHCPLRAMAAKEGSGNQAHRGV

Mouse                         LFQQLLVNHAECQYVRLLRSHCRFRTAN-------------

Rat                           LFQQLLMNHAKCQYVRFLRSHCRFRTAN-------------

Bovine                        LFRKLLGNHARSPYGALLRAHCPLPASAPRAGPDHQKCPGV

Baker's yeast                 TLQKLLKRHKRLNYVSILNSICP------------------

Fission yeast                 LIEQTAKRLHRISLSKVYNHYCPY-----------------
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 – 1132 Telomerase reverse transcriptase
Region 301 – 538 Required for oligomerization
Region 325 – 550 RNA-interacting domain 2
Region 376 – 521 QFP motif
Region 397 – 417 CP motif
Helix 405 – 412



Literature citations
Submission
NIEHS SNPs program;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS TYR-412 AND THR-1062; Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia.
Yamaguchi H.; Calado R.T.; Ly H.; Kajigaya S.; Baerlocher G.M.; Chanock S.J.; Lansdorp P.M.; Young N.S.;
N. Engl. J. Med. 352:1413-1424(2005)
Cited for: VARIANTS PFBMFT1 THR-202; TYR-412; MET-694; CYS-772 AND MET-1090; VARIANTS THR-279; GLU-441 DEL AND THR-1062; Complex inheritance pattern of dyskeratosis congenita in two families with 2 different mutations in the telomerase reverse transcriptase gene.
Du H.Y.; Pumbo E.; Manley P.; Field J.J.; Bayliss S.J.; Wilson D.B.; Mason P.J.; Bessler M.;
Blood 111:1128-1130(2008)
Cited for: VARIANTS DKCB4 TYR-412 AND SER-704; CHARACTERIZATION OF VARIANTS DKCB4 TYR-412 AND SER-704; Defining the pathogenic role of telomerase mutations in myelodysplastic syndrome and acute myeloid leukemia.
Kirwan M.; Vulliamy T.; Marrone A.; Walne A.J.; Beswick R.; Hillmen P.; Kelly R.; Stewart A.; Bowen D.; Schonland S.O.; Whittle A.M.; McVerry A.; Gilleece M.; Dokal I.;
Hum. Mutat. 30:1567-1573(2009)
Cited for: VARIANTS ALA-65; MET-299; LYS-522 AND THR-1062; VARIANTS AA THR-202; TYR-412; GLU-441 DEL; ASN-570; GLN-631; MET-694 AND LEU-785; Constitutional hypomorphic telomerase mutations in patients with acute myeloid leukemia.
Calado R.T.; Regal J.A.; Hills M.; Yewdell W.T.; Dalmazzo L.F.; Zago M.A.; Lansdorp P.M.; Hogge D.; Chanock S.J.; Estey E.H.; Falcao R.P.; Young N.S.;
Proc. Natl. Acad. Sci. U.S.A. 106:1187-1192(2009)
Cited for: VARIANTS ALA-65; MET-299; TYR-412; GLU-441 DEL; LYS-522 AND THR-1062;
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.