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UniProtKB/Swiss-Prot P06753: Variant p.Arg168His

Tropomyosin alpha-3 chain
Gene: TPM3
Chromosomal location: 1q21.2
Variant information

Variant position:  168
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 Histidine (H) at position 168 (R168H, p.Arg168His).
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 medium size and polar (H)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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:  Cap myopathy 1 (CAPM1) [MIM:609284]: A rare congenital skeletal muscle disorder characterized by the presence of cap-like structures which are well demarcated and peripherally located under the sarcolemma and show abnormal accumulation of sarcomeric proteins. Clinical features are early onset of hypotonia and slowly progressive muscle weakness. Respiratory problems are common. {ECO:0000269|PubMed:18300303, ECO:0000269|PubMed:19487656, ECO:0000269|PubMed:19553118, ECO:0000269|PubMed:24239060, ECO:0000269|PubMed:24692096}. 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:  Myopathy, congenital, with fiber-type disproportion (CFTD) [MIM:255310]: A genetically heterogeneous disorder in which there is relative hypotrophy of type 1 muscle fibers compared to type 2 fibers on skeletal muscle biopsy. However, these findings are not specific and can be found in many different myopathic and neuropathic conditions. {ECO:0000269|PubMed:18300303, ECO:0000269|PubMed:19953533, ECO:0000269|PubMed:20951040, ECO:0000269|PubMed:24692096}. 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:  Nemaline myopathy 1 (NEM1) [MIM:609284]: A form of nemaline myopathy with autosomal dominant or recessive inheritance. Nemaline myopathies are disorders characterized by muscle weakness of varying onset and severity, and abnormal thread-like or rod-shaped structures in muscle fibers on histologic examination. Autosomal dominant NEM1 is characterized by a moderate phenotype with onset between birth and early second decade of life. Weakness is diffuse and symmetric with slow progression often with need for a wheelchair in adulthood. The autosomal recessive form has onset at birth with moderate to severe hypotonia and diffuse weakness. In the most severe cases, death can occur before 2 years. Less severe cases have delayed major motor milestones, and these patients may walk, but often need a wheelchair before 10 years. {ECO:0000269|PubMed:10587521, ECO:0000269|PubMed:17376686, ECO:0000269|PubMed:24692096, ECO:0000269|PubMed:7704029}. 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 NEM1, CAPM1 and CFTD; also found in patients with undefined congenital myopathy.
Any additional useful information about the variant.

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



Sequence information

Variant position:  168
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  285
The length of the canonical sequence.

Location on the sequence:   QLKEAKHIAEEADRKYEEVA  R KLVIIEGDLERTEERAELAE
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                         QLKEAKHIAEEADRKYEEVARKLVIIEGDLERTEERAELAE

Mouse                         QLKEAKHIAEEADRKYEEVARKLVIIEGDLERTEERAELAE

Rat                           QLKEAKHIAEEADRKYEEVARKLVIIEGDLERTEERAELAE

Pig                           QLKEAKHIAEEADRKYEEVARKLVIIEGDLERTEERAELAE

Bovine                        QLKEAKHIAEEADRKYEEVARKLVIIEGDLERTEERAELAE

Caenorhabditis elegans        QVDEAKVIAEDADRKYEEVARKLAMVEADLERAEERAEAGE

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 – 285 Tropomyosin alpha-3 chain
Coiled coil 1 – 285


Literature citations

A second pedigree with autosomal dominant nemaline myopathy caused by TPM3 mutation: a clinical and pathological study.
Penisson-Besnier I.; Monnier N.; Toutain A.; Dubas F.; Laing N.;
Neuromuscul. Disord. 17:330-337(2007)
Cited for: VARIANT NEM1 HIS-168;

Mutations in TPM3 are a common cause of congenital fiber type disproportion.
Clarke N.F.; Kolski H.; Dye D.E.; Lim E.; Smith R.L.; Patel R.; Fahey M.C.; Bellance R.; Romero N.B.; Johnson E.S.; Labarre-Vila A.; Monnier N.; Laing N.G.; North K.N.;
Ann. Neurol. 63:329-337(2008)
Cited for: VARIANTS CFTD MET-100; CYS-168; GLY-168; GLU-169 AND GLY-245; VARIANT CAPM1 HIS-168;

A TPM3 mutation causing cap myopathy.
De Paula A.M.; Franques J.; Fernandez C.; Monnier N.; Lunardi J.; Pellissier J.F.; Figarella-Branger D.; Pouget J.;
Neuromuscul. Disord. 19:685-688(2009)
Cited for: VARIANT CAPM1 HIS-168;

Mutations of tropomyosin 3 (TPM3) are common and associated with type 1 myofiber hypotrophy in congenital fiber type disproportion.
Lawlor M.W.; Dechene E.T.; Roumm E.; Geggel A.S.; Moghadaszadeh B.; Beggs A.H.;
Hum. Mutat. 31:176-183(2010)
Cited for: VARIANTS CFTD VAL-4; PRO-91; HIS-168 AND LYS-241;

Congenital fibre type disproportion associated with mutations in the tropomyosin 3 (TPM3) gene mimicking congenital myasthenia.
Munot P.; Lashley D.; Jungbluth H.; Feng L.; Pitt M.; Robb S.A.; Palace J.; Jayawant S.; Kennet R.; Beeson D.; Cullup T.; Abbs S.; Laing N.; Sewry C.; Muntoni F.;
Neuromuscul. Disord. 20:796-800(2010)
Cited for: VARIANTS CFTD HIS-168 AND ALA-174;

Mutation update and genotype-phenotype correlations of novel and previously described mutations in TPM2 and TPM3 causing congenital myopathies.
Marttila M.; Lehtokari V.L.; Marston S.; Nyman T.A.; Barnerias C.; Beggs A.H.; Bertini E.; Ceyhan-Birsoy O.; Cintas P.; Gerard M.; Gilbert-Dussardier B.; Hogue J.S.; Longman C.; Eymard B.; Frydman M.; Kang P.B.; Klinge L.; Kolski H.; Lochmueller H.; Magy L.; Manel V.; Mayer M.; Mercuri E.; North K.N.; Peudenier-Robert S.; Pihko H.; Probst F.J.; Reisin R.; Stewart W.; Taratuto A.L.; de Visser M.; Wilichowski E.; Winer J.; Nowak K.; Laing N.G.; Winder T.L.; Monnier N.; Clarke N.F.; Pelin K.; Groenholm M.; Wallgren-Pettersson C.;
Hum. Mutat. 35:779-790(2014)
Cited for: VARIANTS NEM1 PHE-88 AND CYS-168; VARIANTS CAPM1 PHE-88; ALA-151; CYS-168 AND ILE-245; VARIANTS CFTD VAL-100; CYS-168 AND HIS-168; VARIANTS CYS-91 AND LYS-253;

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.