UniProtKB/SwissProt variant VAR

Variant information

Variant position:

170

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 170 (V170M, p.Val170Met).

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; the mutant protein is demonstrated to cause decreased telomerase activity.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs387907248 [ dbSNP | Ensembl ]

Sequence information

Variant position:

170

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:

VHLLARCALFVLVAPSCAYQ V CGPPLYQLGAATQARPPPHA

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                         VHLLARCALFVLVAPSCAYQVCGPPLYQLGAAT------QA--RPPPHA

                              THLLARCALYLLVAPSCAYQVCGPPLYDLCAPA------SL

Mouse                         VYLLAHCALYLLVPPSCAYQVCGSPLYQICATTDIWPSVSA

Rat                           VYLLSHCALYLLVPPSCAYQVCGSPLYQICATTDTWSSVPA

Bovine                        THLLSRCALYLLVPPTCAYQVCGPPLYDLRAAA------AA

Baker's yeast                 VDLLINYTV-IQFNGQFFTQIVG------------------

Fission yeast                 HYLLSKGSIFEALPNDNYLQISGIPLF--------------

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
Region	1 – 230	RNA-interacting domain 1
Region	58 – 197	GQ motif
Site	169 – 169	Required for optimal binding of telomeric ssDNA and incorporation of nucleotides at the second position of the template
Mutagenesis	169 – 169	Q -> A. About 80% loss of enzymatic activity. Greatly reduced incorporation of second nucleotide. Altered strength of binding to ssDNA. Little effect on repeat addition processivity, nor on TR interaction nor on protein levels.
Mutagenesis	169 – 169	Q -> N. About 85% loss of enzymatic activity. Greatly reduced incorporation of second nucleotide. Altered strength of binding to ssDNA. No effect on protein levels nor on TR interaction.
Mutagenesis	169 – 169	Q -> T. About 90% loss of enzymatic activity. Greatly reduced incorporation of second nucleotide. Altered strength of binding to ssDNA. No effect on protein levels nor on TR interaction.

Literature citations

Syndrome complex of bone marrow failure and pulmonary fibrosis predicts germline defects in telomerase.
Parry E.M.; Alder J.K.; Qi X.; Chen J.J.; Armanios M.;
Blood 117:5607-5611(2011)
Cited for: VARIANTS PFBMFT1 MET-170; THR-716; PHE-841; ARG-902 AND PHE-1025; CHARACTERIZATION OF VARIANTS PFBMFT1 MET-170; THR-716; PHE-841 AND PHE-1025;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O14746: Variant p.Val170Met