UniProtKB/SwissProt variant VAR

Variant information

Variant position:

791

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

Type of variant:

Disease [Disclaimer]

The variants are classified into three categories: Disease, Polymorphism and Unclassified.

Disease: Variants implicated in disease according to literature reports.
Polymorphism: Variants not reported to be implicated in disease.
Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:

From Valine (V) to Isoleucine (I) at position 791 (V791I, p.Val791Ile).

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

Involvement in disease:

Pulmonary fibrosis, and/or bone marrow failure, telomere-related, 1 (PFBMFT1) [MIM:614742]: A disease associated with shortened telomeres. Pulmonary fibrosis is the most common manifestation. Other manifestations include aplastic anemia due to bone marrow failure, hepatic fibrosis, and increased cancer risk, particularly myelodysplastic syndrome and acute myeloid leukemia. Phenotype, age at onset, and severity are determined by telomere length. {ECO:0000269|PubMed:15814878, ECO:0000269|PubMed:17460043, ECO:0000269|PubMed:21436073, ECO:0000269|PubMed:21483807, ECO:0000269|PubMed:22512499}. Note=The disease is caused by mutations affecting the gene represented in this entry.

The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:

In PFBMFT1; associated with Met-867 in cis on the same allele; the double mutant shows severe defects in telomere repeat addition processivity.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs141425941 [ dbSNP | Ensembl ]

Sequence information

Variant position:

791

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:

PYMRQFVAHLQETSPLRDAV V IEQSSSLNEASSGLFDVFLR

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                         PYMRQFVAHLQET--SPLRDAVVIEQSSSLNEASSGLFDVFLR

                              PYMRQFVERLQET--SLLRDAVVIEQSSSLNEAGSSLFHLF

Mouse                         PYMGQFLKHLQDSDASALRNSVVIEQSISMNESSSSLFDFF

Rat                           PYMGQFTKHLQDSDASALRNSVVIEQSISMNETGSSLLHFF

Bovine                        PYLRQLVEHLQAM--GSLRDAVVIEQSCSLNEPGSSLFNLF

Baker's yeast                 PYE------------------LYIDNVRTVHLSNQDVINVV

Fission yeast                 PFEK--VVQLLSM---KTSDTLFVDFVDYWTKSSSEIFKML

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
Alternative sequence	764 – 807	STLTDLQPYMRQFVAHLQETSPLRDAVVIEQSSSLNEASSGLFD -> LRPVPGDPAGLHPLHAALQPVLRRHGEQAVCGDSAGRAAPAFGG. In isoform 2 and isoform 4.

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;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O14746: Variant p.Val791Ile