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UniProtKB/Swiss-Prot P12883: Variant p.Arg719Trp

Myosin-7
Gene: MYH7
Chromosomal location: 14q12
Variant information

Variant position:  719
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 719 (R719W, p.Arg719Trp).
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:  Cardiomyopathy, familial hypertrophic 1 (CMH1) [MIM:192600]: A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. {ECO:0000269|PubMed:10065021, ECO:0000269|PubMed:10329202, ECO:0000269|PubMed:10521296, ECO:0000269|PubMed:10563488, ECO:0000269|PubMed:10679957, ECO:0000269|PubMed:10862102, ECO:0000269|PubMed:11113006, ECO:0000269|PubMed:11133230, ECO:0000269|PubMed:11214007, ECO:0000269|PubMed:11424919, ECO:0000269|PubMed:11733062, ECO:0000269|PubMed:11861413, ECO:0000269|PubMed:11968089, ECO:0000269|PubMed:12081993, ECO:0000269|PubMed:12566107, ECO:0000269|PubMed:12590187, ECO:0000269|PubMed:12707239, ECO:0000269|PubMed:12818575, ECO:0000269|PubMed:12820698, ECO:0000269|PubMed:12951062, ECO:0000269|PubMed:12974739, ECO:0000269|PubMed:12975413, ECO:0000269|PubMed:1417858, ECO:0000269|PubMed:15358028, ECO:0000269|PubMed:15483641, ECO:0000269|PubMed:1552912, ECO:0000269|PubMed:15563892, ECO:0000269|PubMed:15856146, ECO:0000269|PubMed:15858117, ECO:0000269|PubMed:16199542, ECO:0000269|PubMed:16267253, ECO:0000269|PubMed:1638703, ECO:0000269|PubMed:16650083, ECO:0000269|PubMed:16938236, ECO:0000269|PubMed:17095604, ECO:0000269|PubMed:17372140, ECO:0000269|PubMed:18175163, ECO:0000269|PubMed:18403758, ECO:0000269|PubMed:1975517, ECO:0000269|PubMed:25182012, ECO:0000269|PubMed:7581410, ECO:0000269|PubMed:7731997, ECO:0000269|PubMed:7848441, ECO:0000269|PubMed:7874131, ECO:0000269|PubMed:8250038, ECO:0000269|PubMed:8254035, ECO:0000269|PubMed:8268932, ECO:0000269|PubMed:8282798, ECO:0000269|PubMed:8343162, ECO:0000269|PubMed:8435239, ECO:0000269|PubMed:8483915, ECO:0000269|PubMed:8655135, ECO:0000269|PubMed:8899546, ECO:0000269|PubMed:9544842, ECO:0000269|PubMed:9822100, ECO:0000269|PubMed:9829907}. 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 CMH1.
Any additional useful information about the variant.

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



Sequence information

Variant position:  719
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1935
The length of the canonical sequence.

Location on the sequence:   LEGIRICRKGFPNRILYGDF  R QRYRILNPAAIPEGQFIDSR
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                         LEGIRICRKGFPNRILYGDFRQRYRILNPAAIPEGQFIDSR

                              LEGIRICRKGFPNRILYGDFRQRYRILNPAAIPEGQFIDSR

Mouse                         LEGIRICRKGFPNRILYGDFRQRYRILNPAAIPEGQFIDSR

Rat                           LEGIRICRKGFPNRILYGDFRQRYRILNPAAIPEGQFIDSR

Pig                           LEGIRICRKGFPNRILYGDFRQRYRILNPAAIPEGQFIDSR

Bovine                        LEGIRICRKGFPNRILYGDFRQRYRILNPAAIPEGQFIDSR

Horse                         LEGIRICRKGFPNRILYGDFRQRYRILNPAAIPEGQFIDSR

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 – 1935 Myosin-7
Domain 85 – 778 Myosin motor
Helix 715 – 722


Literature citations

Isolation of a de novo mutant myocardial beta MHC protein in a pedigree with hypertrophic cardiomyopathy.
Greve G.; Bachinski L.; Friedman D.L.; Czernuzewicz G.; Anan R.; Towbin J.A.; Seidman C.E.; Roberts R.;
Hum. Mol. Genet. 3:2073-2075(1994)
Cited for: VARIANT CMH1 TRP-719;

Prognostic implications of novel beta cardiac myosin heavy chain gene mutations that cause familial hypertrophic cardiomyopathy.
Anan R.; Greve G.; Thierfelder L.; Watkins H.; McKenna W.; Solomon S.; Vecchio C.; Shono H.; Nakao S.; Tanaka H.; Mares A. Jr.; Towbin J.A.; Spirito P.; Roberts R.; Seidman J.G.; Seidman C.E.;
J. Clin. Invest. 93:280-285(1994)
Cited for: VARIANTS CMH1 CYS-513; ARG-716 AND TRP-719;

A high risk phenotype of hypertrophic cardiomyopathy associated with a compound genotype of two mutated beta-myosin heavy chain genes.
Jeschke B.; Uhl K.; Weist B.; Schroder D.; Meitinger T.; Dohlemann C.; Vosberg H.-P.;
Hum. Genet. 102:299-304(1998)
Cited for: VARIANTS CMH1 THR-349 AND TRP-719;

Genotype-phenotype analysis in four families with mutations in beta-myosin heavy chain gene responsible for familial hypertrophic cardiomyopathy.
Tesson F.; Richard P.; Charron P.; Mathieu B.; Cruaud C.; Carrier L.; Dubourg O.; Lautie N.; Desnos M.; Millaire A.; Isnard R.; Hagege A.A.; Bouhour J.-B.; Bennaceur M.; Hainque B.; Guicheney P.; Schwartz K.; Komajda M.;
Hum. Mutat. 12:385-392(1998)
Cited for: VARIANTS CMH1 THR-263; TRP-719; CYS-723 AND GLU-930 DEL;

The cardiac beta-myosin heavy chain gene is not the predominant gene for hypertrophic cardiomyopathy in the Finnish population.
Jaeaeskelaeinen P.; Soranta M.; Miettinen R.; Saarinen L.; Pihlajamaeki J.; Silvennoinen K.; Tikanoja T.; Laakso M.; Kuusisto J.;
J. Am. Coll. Cardiol. 32:1709-1716(1998)
Cited for: VARIANTS CMH1 SER-696 AND TRP-719;

Assessment of diastolic function with Doppler tissue imaging to predict genotype in preclinical hypertrophic cardiomyopathy.
Ho C.Y.; Sweitzer N.K.; McDonough B.; Maron B.J.; Casey S.A.; Seidman J.G.; Seidman C.E.; Solomon S.D.;
Circulation 105:2992-2997(2002)
Cited for: VARIANTS CMH1 HIS-663; TRP-719; ARG-768 AND GLY-906;

Low-density DNA microarrays are versatile tools to screen for known mutations in hypertrophic cardiomyopathy.
Waldmueller S.; Freund P.; Mauch S.; Toder R.; Vosberg H.-P.;
Hum. Mutat. 19:560-569(2002)
Cited for: VARIANTS CMH1 GLN-249; THR-349; GLN-403; ARG-595; MET-606; GLN-719; TRP-719; GLU-927 DEL AND LYS-1555;

Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy.
Richard P.; Charron P.; Carrier L.; Ledeuil C.; Cheav T.; Pichereau C.; Benaiche A.; Isnard R.; Dubourg O.; Burban M.; Gueffet J.-P.; Millaire A.; Desnos M.; Schwartz K.; Hainque B.; Komajda M.;
Circulation 107:2227-2232(2003)
Cited for: VARIANTS CMH1 MET-39; ASN-188; HIS-204; SER-232; GLN-249; THR-263; THR-355; LEU-403; GLN-403; TRP-403; VAL-428; THR-443; CYS-453; SER-479; LYS-483; MET-606; ILE-659; SER-663; HIS-663; CYS-671; ARG-716; GLN-719; TRP-719; CYS-723; GLU-733; ARG-741; ARG-768; GLU-778; HIS-787; THR-852; GLY-869; GLU-883 DEL; GLU-930 DEL; ARG-1135; GLN-1218; MET-1377; THR-1379; TRP-1382 AND THR-1777; VARIANT MET-1692;

Mutation spectrum in a large cohort of unrelated consecutive patients with hypertrophic cardiomyopathy.
Erdmann J.; Daehmlow S.; Wischke S.; Senyuva M.; Werner U.; Raible J.; Tanis N.; Dyachenko S.; Hummel M.; Hetzer R.; Regitz-Zagrosek V.;
Clin. Genet. 64:339-349(2003)
Cited for: VARIANTS CMH1 TRP-143; TRP-403; ILE-411; SER-584; HIS-694; TRP-719; THR-736; PHE-796; ILE-824; HIS-870; PHE-905; GLN-924 AND ASN-928;

Denaturing high performance liquid chromatography: high throughput mutation screening in familial hypertrophic cardiomyopathy and SNP genotyping in motor neurone disease.
Yu B.; Sawyer N.A.; Caramins M.; Yuan Z.G.; Saunderson R.B.; Pamphlett R.; Richmond D.R.; Jeremy R.W.; Trent R.J.;
J. Clin. Pathol. 58:479-485(2005)
Cited for: VARIANTS CMH1 VAL-227; GLY-328; GLU-351; GLN-403; TRP-403; ILE-411; THR-435; CYS-453; HIS-453; MET-606; CYS-663; GLN-719; TRP-719; HIS-787; GLY-894; VAL-908 AND LYS-927; VARIANT CYS-1519;

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.