UniProtKB/SwissProt variant VAR

Variant information

Variant position:

694

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 Valine (V) to Methionine (M) at position 694 (V694M, p.Val694Met).

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:

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:

In PFBMFT1 and AA; moderate.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121918662 [ dbSNP | Ensembl ]

Sequence information

Variant position:

694

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:

1132

The length of the canonical sequence.

Location on the sequence:

GLLGASVLGLDDIHRAWRTF V LRVRAQDPPPELYFVKVDVT

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                         GLLGASVLGLDDIHRAWRTF---VLRVRAQDPPPELYFVKVDVT

                              SLLGASMLGMDDIHRAWRTF---VLRIRAQNPAPQLYFVKV

Mouse                         HLMGSSVLGMNDIYRTWRAF---VLRVRALDQTPRMYFVKA

Rat                           NLMGASVLGTSDSYRIWRTF---VLRVRALDQTPRMYFVKA

Bovine                        GLLGASVLGMDDIHRAWRAF---VLPLRARGPAPPLYFVKV

Baker's yeast                 TSF-TKIYSPTQIADRIKEFKQRLLK-KFNNVLPELYFMKF

Fission yeast                 SGIPFNL----EVYMKLLTFKKDLLKHRMFGR--KKYFVRI

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 – 1132	Telomerase reverse transcriptase
Domain	605 – 935	Reverse transcriptase
Metal binding	712 – 712	Magnesium; catalytic
Modified residue	707 – 707	Phosphotyrosine; by SRC-type Tyr-kinases
Mutagenesis	707 – 707	Y -> F. Abolishes oxidative stress-induced phosphorylation and RAN binding. Impaired nuclear export and enhanced antiapoptotic activity against ROS-dependent apoptosis induction. Impaired interaction with PTPN11. No dephosphorylation by PTPN11.
Mutagenesis	712 – 712	D -> A. Loss of telomerase activity. In the absence of TR, no loss of binding to telomeric primers.

Literature citations

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;

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;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O14746: Variant p.Val694Met