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UniProtKB/Swiss-Prot P11055: Variant p.Thr178Ile

Myosin-3
Gene: MYH3
Variant information

Variant position:  178
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 Threonine (T) to Isoleucine (I) at position 178 (T178I, p.Thr178Ile).
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 medium size and hydrophobic (I)
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

Involvement in disease:  Arthrogryposis, distal, 2A (DA2A) [MIM:193700]: A form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. DA2A is characterized by contractures of the hands and feet, oropharyngeal abnormalities, scoliosis, and a distinctive face that includes a very small oral orifice, puckered lips, and a H-shaped dimple of the chin. {ECO:0000269|PubMed:16642020, ECO:0000269|PubMed:18695058}. 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.

Involvement in disease:  Arthrogryposis, distal, 2B3 (DA2B3) [MIM:618436]: A form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. Distal arthrogryposis type 2 is characterized by contractures of the hands and feet, and a distinctive face characterized by prominent nasolabial folds, small mouth and downslanting palpebral fissures. DA2B3 inheritance is autosomal dominant. {ECO:0000269|PubMed:16642020, ECO:0000269|PubMed:18695058}. 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 DA2A and DA2B3.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  178
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1940
The length of the canonical sequence.

Location on the sequence:   ISDNAYQFMLTDRENQSILI  T GESGAGKTVNTKRVIQYFAT
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.

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 1 – 1940 Myosin-3
Domain 86 – 779 Myosin motor


Literature citations

Mutations in embryonic myosin heavy chain (MYH3) cause Freeman-Sheldon syndrome and Sheldon-Hall syndrome.
Toydemir R.M.; Rutherford A.; Whitby F.G.; Jorde L.B.; Carey J.C.; Bamshad M.J.;
Nat. Genet. 38:561-565(2006)
Cited for: INVOLVEMENT IN DA2A; INVOLVEMENT IN DA2B3; VARIANTS DA2A ILE-178; GLY-498; SER-583; CYS-672; HIS-672 AND ASP-825; VARIANTS DA2B3 ILE-178; PHE-261; CYS-292; LYS-375; TYR-517; VAL-769 AND GLU-838; LEU-841 DEL; VARIANTS ALA-1622 AND VAL-1637;

Embryonic myosin heavy-chain mutations cause distal arthrogryposis and developmental myosin myopathy that persists postnatally.
Tajsharghi H.; Kimber E.; Kroksmark A.K.; Jerre R.; Tulinius M.; Oldfors A.;
Arch. Neurol. 65:1083-1090(2008)
Cited for: INVOLVEMENT IN DA2B3; VARIANT DA2A ILE-178; VARIANTS DA2B3 THR-234 AND GLY-462;

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.