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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O14746: Variant p.Val867Met

Telomerase reverse transcriptase
Gene: TERT
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Variant information Variant position: help 867 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 Valine (V) to Methionine (M) at position 867 (V867M, p.Val867Met). 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 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: 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 PFBMFT1; associated with Ile-791 in cis on the same allele; the double mutant shows severe defects in telomere repeat addition processivity; this mutation causes most if not all of the functional defects. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 867 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 GDMENKLFAGIRRDGLLLRL V DDFLLVTPHLTHAKTFLRTL 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                         GDME---NKLFAGIRRDG-LLLRLVDDFLLVTPHLTHAKTFLRTL

                              GDME---RRLFPGIEQDG-VLLRLVDDFLLVTPHLTQAQAF

Mouse                         GDME---NKLFAEVQRDG-LLLRFVDDFLLVTPHLDQAKTF

Rat                           GDME---NKLFAEVQQDG-LLLRFVDDFLLVTPHLAHAKAF

Bovine                        GDME---NKLFPGVQQDG-VLLRLVDDFLLVTPHLTRARDF

Baker's yeast                 DDLLEFYSEFKASPSQDT-LILKLADDFLIISTDQQQVINI

Fission yeast                 EDLI---DEYLSFTKKKGSVLLRVVDDFLFITVNKKDAKKF
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
Domain 605 – 935 Reverse transcriptase
Binding site 868 – 868
Binding site 869 – 869
Site 867 – 867 Required for nucleotide incorporation and primer extension rate
Alternative sequence 808 – 1132 Missing. In isoform 2 and isoform 4.
Mutagenesis 866 – 866 L -> Y. Moderate reduction in telomerase activity, no change in repeat extension rate nor on nucleotide incorporation fidelity. Little further reduction in activity but 13.5-fold increase in nucleotide incorporation fidelity; when associated with M-867.
Mutagenesis 867 – 867 V -> A. About 75% reduction in telomerase activity, about 80% reduction in repeat reduction rate and 3.9-fold increase in nucleotide incorporation fidelity.
Mutagenesis 867 – 867 V -> M. About 75% reduction in telomerase activity, about 50% reduction in repeat extension rate and 5.2-fold increase in nucleotide incorporation fidelity. Little further reduction in activity and 13.5-fold increase in nucleotide incorporation fidelity; when associated with Y-866.
Mutagenesis 867 – 867 V -> T. Severe reduction in telomerase activity, about 50% reduction in repeat extension rate and 2.2-fold increase in nucleotide incorporation fidelity. No further reduction in activity but 2.8-fold increase in nucleotide incorporation fidelity; when associated with Y-866.
Mutagenesis 868 – 868 D -> A. Loss of telomerase activity.
Mutagenesis 869 – 869 D -> A. Loss of telomerase activity.
Beta strand 861 – 873



Literature citations
Ancestral mutation in telomerase causes defects in repeat addition processivity and manifests as familial pulmonary fibrosis.
Alder J.K.; Cogan J.D.; Brown A.F.; Anderson C.J.; Lawson W.E.; Lansdorp P.M.; Phillips J.A. III; Loyd J.E.; Chen J.J.; Armanios M.;
PLoS Genet. 7:E1001352-E1001352(2011)
Cited for: VARIANTS PFBMFT1 ILE-791 AND MET-867; CHARACTERIZATION OF VARIANTS PFBMFT1 ILE-791 AND MET-867;
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.