UniProtKB/Swiss-Prot P02766: Variant p.Ala65Asp

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

Variant position:  65
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 Alanine (A) to Aspartate (D) at position 65 (A65D, p.Ala65Asp).
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 small size and hydrophobic (A) to medium size and acidic (D)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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:  Amyloidosis, transthyretin-related (AMYL-TTR) [MIM:105210]: A hereditary generalized amyloidosis due to transthyretin amyloid deposition. Protein fibrils can form in different tissues leading to amyloid polyneuropathies, amyloidotic cardiomyopathy, carpal tunnel syndrome, systemic senile amyloidosis. The disease includes leptomeningeal amyloidosis that is characterized by primary involvement of the central nervous system. Neuropathologic examination shows amyloid in the walls of leptomeningeal vessels, in pia arachnoid, and subpial deposits. Some patients also develop vitreous amyloid deposition that leads to visual impairment (oculoleptomeningeal amyloidosis). Clinical features include seizures, stroke-like episodes, dementia, psychomotor deterioration, variable amyloid deposition in the vitreous humor. 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 AMYL-TTR; amyloid cardiomyopathy.
Any additional useful information about the variant.



Sequence information

Variant position:  65
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:   AINVAVHVFRKAADDTWEPF  A SGKTSESGELHGLTTEEEFV
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                         AINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFV

Chimpanzee                    AINVAVHVFKKAADETWEPFASGKTSESGELHGLTTEEEFV

Mouse                         AVDVAVKVFKKTSEGSWEPFASGKTAESGELHGLTTDEKFV

Rat                           AVDVAVKVFKKTADGSWEPFASGKTAESGELHGLTTDEKFT

Pig                           AVNVGVKVFKKAADGTWEPFALGKTSEFGELHGLTTDEKFV

Bovine                        AANVGVKVFKKAADETWEPFASGKTSESGELHGLTTEDKFV

Rabbit                        AVDVSVHVFKKAADETWEPFASGKTSKTGELHGLTTSEKFV

Sheep                         AANVGVKVFKKAADETWEPFASGKTSDSGELHGLTTEDKFV

Chicken                       AANVAVKVFKKAADGTWQDFATGKTTEFGEIHELTTEEQFV

Xenopus laevis                AANLLVNVFRQTESGKWEQITSGKTTELGEIHNLTTDEQFT

Xenopus tropicalis            AANLLVQVFRNT-EGNWELISSGKTTELGEIHNIITDEQFT

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 61 – 68


Literature citations

No reference for the current variant in UniProtKB/Swiss-Prot.

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.