UniProtKB/Swiss-Prot P02766: Variant p.Thr80Ala

Transthyretin
Gene: TTR
Chromosomal location: 18q12.1
Variant information

Variant position:  80
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Threonine (T) to Alanine (A) at position 80 (T80A, p.Thr80Ala).
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:  Change from medium size and polar (T) to small size and hydrophobic (A)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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 AMYL-TTR; amyloid polyneuropathy and cardiomyopathy.
Any additional useful information about the variant.



Sequence information

Variant position:  80
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  147
The length of the canonical sequence.

Location on the sequence:   TWEPFASGKTSESGELHGLT  T EEEFVEGIYKVEIDTKSYWK
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                         TWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWK

Chimpanzee                    TWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWK

Mouse                         SWEPFASGKTAESGELHGLTTDEKFVEGVYRVELDTKSYWK

Rat                           SWEPFASGKTAESGELHGLTTDEKFTEGVYRVELDTKSYWK

Pig                           TWEPFALGKTSEFGELHGLTTDEKFVEGIYKVELDTKSYWK

Bovine                        TWEPFASGKTSESGELHGLTTEDKFVEGLYKVELDTKSYWK

Rabbit                        TWEPFASGKTSKTGELHGLTTSEKFVEGVYKVELDTKSYWK

Sheep                         TWEPFASGKTSDSGELHGLTTEDKFVEGLYKVELDTKSYWK

Chicken                       TWQDFATGKTTEFGEIHELTTEEQFVEGVYRVEFDTSSYWK

Xenopus laevis                KWEQITSGKTTELGEIHNLTTDEQFTEGVYKIEFATKAFWG

Xenopus tropicalis            NWELISSGKTTELGEIHNIITDEQFTEGVYKIEFATKTFWR

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.

TypePositionsDescription
Chain 21 – 147 Transthyretin
Binding site 74 – 74 Thyroid hormones
Modified residue 62 – 62 4-carboxyglutamate; in a patient with Moyamoya disease
Beta strand 77 – 80


Literature citations

Transthyretin gene analysis in European patients with suspected familial amyloid polyneuropathy.
Reilly M.M.; Adams D.; Booth D.R.; Davis M.B.; Said G.; Laubriat-Bianchin M.; Pepys M.B.; Thomas P.K.; Harding A.E.;
Brain 118:849-856(1995)
Cited for: VARIANTS AMYL-TTR MET-50; ASN-55; ALA-69; ARG-70; ALA-80; TYR-97 AND GLN-109;

Misdiagnosis of hereditary amyloidosis as AL (primary) amyloidosis.
Lachmann H.J.; Booth D.R.; Booth S.E.; Bybee A.; Gilbertson J.A.; Gillmore J.D.; Pepys M.B.; Hawkins P.N.;
N. Engl. J. Med. 346:1786-1791(2002)
Cited for: VARIANTS AMYL-TTR MET-50; LEU-53; VAL-53; VAL-58; GLU-67; ALA-80; SER-140 AND ILE-142;

Identification of transthyretin variants by sequential proteomic and genomic analysis.
Bergen H.R. III; Zeldenrust S.R.; Butz M.L.; Snow D.S.; Dyck P.J.; Dyck P.J.B.; Klein C.J.; O'Brien J.F.; Thibodeau S.N.; Muddiman D.C.;
Clin. Chem. 50:1544-1552(2004)
Cited for: VARIANTS SER-26; CYS-53 AND ALA-114; VARIANTS AMYL-TTR GLU-67; HIS-78; ALA-80 AND TYR-97; IDENTIFICATION BY MASS SPECTROMETRY;

Genetic microheterogeneity of human transthyretin detected by IEF.
Altland K.; Benson M.D.; Costello C.E.; Ferlini A.; Hazenberg B.P.C.; Hund E.; Kristen A.V.; Linke R.P.; Merlini G.; Salvi F.; Saraiva M.J.; Singer R.; Skinner M.; Winter P.;
Electrophoresis 28:2053-2064(2007)
Cited for: VARIANTS AMYL-TTR PRO-32; ILE-40; SER-44; ALA-50; MET-50; LEU-53; VAL-53; PRO-56; THR-65; ALA-67; ALA-69; ILE-69; ALA-80; LEU-84; LEU-88; ALA-91; TYR-97; PHE-98; SER-104; ASN-104; THR-104; ALA-114; GLY-117; ASN-126; MET-127; VAL-127; MET-131 AND ILE-142; VARIANTS ILE-33; SER-121 AND THR-129; VARIANT CHICAGO MET-139;

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.