UniProtKB/Swiss-Prot Q14204: Variant p.Tyr970Cys

Cytoplasmic dynein 1 heavy chain 1
Gene: DYNC1H1
Chromosomal location: 14q32
Variant information

Variant position:  970
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 Tyrosine (Y) to Cysteine (C) at position 970 (Y970C, p.Tyr970Cys).
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 large size and aromatic (Y) to medium size and polar (C)
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:  Spinal muscular atrophy, lower extremity-predominant 1, autosomal dominant (SMALED1) [MIM:158600]: A form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. SMALED1 is characterized by muscle weakness predominantly affecting the proximal lower extremities. 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 SMALED1.
Any additional useful information about the variant.



Sequence information

Variant position:  970
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  4646
The length of the canonical sequence.

Location on the sequence:   GGEPKIKNVVHELRITNQVI  Y LNPPIEECRYKLYQEMFAWK
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                         GGEPKIKNVVHELRITNQVIYLNPPIEECRYKLYQEMFAWK

Mouse                         GGEPKIKNVVHELRITNQVIYLNPPIEECRYKLYQEMFAWK

Rat                           GGEPKIKNVVHELRITNQVIYLNPPIEECRYKLYQEMFAWK

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 2 – 4646 Cytoplasmic dynein 1 heavy chain 1
Region 53 – 1867 Stem


Literature citations

Mutations in the tail domain of DYNC1H1 cause dominant spinal muscular atrophy.
Harms M.B.; Ori-McKenney K.M.; Scoto M.; Tuck E.P.; Bell S.; Ma D.; Masi S.; Allred P.; Al-Lozi M.; Reilly M.M.; Miller L.J.; Jani-Acsadi A.; Pestronk A.; Shy M.E.; Muntoni F.; Vallee R.B.; Baloh R.H.;
Neurology 78:1714-1720(2012)
Cited for: VARIANTS SMALED1 LEU-584; GLU-671 AND CYS-970; CHARACTERIZATION OF VARIANT SMALED1 LEU-584;

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.