UniProtKB/Swiss-Prot P13533: Variant p.Arg721Trp

Gene: MYH6
Chromosomal location: 14q12
Variant information

Variant position:  721
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 Arginine (R) to Tryptophan (W) at position 721 (R721W, p.Arg721Trp).
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 basic (R) to large size and aromatic (W)
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:  Sick sinus syndrome 3 (SSS3) [MIM:614090]: The term 'sick sinus syndrome' encompasses a variety of conditions caused by sinus node dysfunction. The most common clinical manifestations are syncope, presyncope, dizziness, and fatigue. Electrocardiogram typically shows sinus bradycardia, sinus arrest, and/or sinoatrial block. Episodes of atrial tachycardias coexisting with sinus bradycardia ('tachycardia-bradycardia syndrome') are also common in this disorder. SSS occurs most often in the elderly associated with underlying heart disease or previous cardiac surgery, but can also occur in the fetus, infant, or child without heart disease or other contributing factors. {ECO:0000269|PubMed:21378987}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. The lifetime risk of being diagnosed with sick sinus syndrome is higher for carriers of variant p.Arg721Trp than for non-carriers. {ECO:0000269|PubMed:21378987}.
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 SSS3; rare variant predisposing to sick sinus syndrome.
Any additional useful information about the variant.

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

Sequence information

Variant position:  721
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1939
The length of the canonical sequence.

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.




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.

Chain 1 – 1939 Myosin-6
Domain 85 – 780 Myosin motor

Literature citations

A rare variant in MYH6 is associated with high risk of sick sinus syndrome.
Holm H.; Gudbjartsson D.F.; Sulem P.; Masson G.; Helgadottir H.T.; Zanon C.; Magnusson O.T.; Helgason A.; Saemundsdottir J.; Gylfason A.; Stefansdottir H.; Gretarsdottir S.; Matthiasson S.E.; Thorgeirsson G.M.; Jonasdottir A.; Sigurdsson A.; Stefansson H.; Werge T.; Rafnar T.; Kiemeney L.A.; Parvez B.; Muhammad R.; Roden D.M.; Darbar D.; Thorleifsson G.; Walters G.B.; Kong A.; Thorsteinsdottir U.; Arnar D.O.; Stefansson K.;
Nat. Genet. 43:316-320(2011)

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.